Treatment Of Idiopathic Nephrotic Syndrome Research Articles

Initial Treatment of Idiopathic Nephrotic Syndrome in Children with Mycophenolate Mofetil vs. Prednisone: A Prospective, Randomized, Controlled, Multicenter, Open, Phase 3, Noninferiority Study

Initial Treatment of Idiopathic Nephrotic Syndrome in Children with Mycophenolate Mofetil vs. Prednisone: A Prospective, Randomized, Controlled, Multicenter, Open, Phase 3, Noninferiority Study

Saliva monitoring of prednisolone in children with first onset steroid-sensitive nephrotic syndrome: Is it possible?

Prednisolone is the cornerstone of treatment for idiopathic nephrotic syndrome in children, but is associated with marked side-effects. Therapeutic drug monitoring using saliva would be a patient-friendly option to monitor prednisolone treatment. To assess the feasibility of saliva monitoring, we described the pharmacokinetics (PK) of unbound prednisolone in plasma and saliva of children with first onset steroid-sensitive nephrotic syndrome (SSNS). Children (age 2-16 years) with SSNS participating in a randomized, placebo-controlled trial with levamisole were treated with an 18-week tapering schedule of prednisolone. Five serial samples were collected at 4 (saliva) and 8weeks (saliva and plasma) after first onset. A nonlinear mixed-effects model was used to estimate the PK parameters of unbound prednisolone and the saliva-to-plasma ratio. Monte Carlo simulations were performed to assess the predictive performance of saliva monitoring. From 39 children, 109 plasma and 275 saliva samples were available. Estimates (relative squared error) of unbound plasma clearance and volume of distribution were 93 (5%) L h-1 70 kg-1 and 158 (7%) L 70 kg-1, respectively. Typical saliva-to-plasma ratio was 1.30 (8%). Monte Carlo simulations demonstrated that on basis of 4 saliva samples and a single plasma sample unbound plasma area-under-the-concentration-time curve can be predicted within 20% imprecision in 79% of the patients compared to 87% based on 4 plasma samples. Saliva proved to be a reliable and patient-friendly option to determine prednisolone plasma exposure in children with SSNS. This opens opportunities for further PK and pharmacodynamics studies of prednisolone in a variety of paediatric conditions.

Repeated implants failure in young patient with idiopathic nephrotic syndrome: a case report with brief review of the literature

BackgroundNephrotic syndrome is a chronic disorder characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic minimal-change disease is the most common form encountered in children. Corticosteroids are the cornerstone for the treatment of idiopathic nephrotic syndrome (INS), with different regimens depending on the response to therapy and frequency of relapses. This case report presents complications after implant treatment in patient with INS.Case presentation20 years old female patient presented for implant consultation. Medical history includes INS since early childhood, and she is on different medications to control her condition, including long-term steroid use. Dental history revealed that implant treatment was unsuccessful after multiple attempts. She presented with an implant on the area of lower left first mandibular molar, that shows increased mobility and radiolucency on radiographic examination. A diagnosis of implant failure was made, the implant was removed, and the area was cleaned and sutured. The patient decided to replace her missing teeth with fixed partial denture and was referred for prosthodontist. The potential adverse effect of steroid use and the possible underlying mechanism that could affect bone metabolism and implants osseointegration are reviewed.ConclusionClinical practice guidelines are needed for the management of dental implants in chronic steroid users.

Levamisole suppresses activation and proliferation of human T cells by the induction of a p53-dependent DNA damage response.

Levamisole (LMS) is a small molecule used in the treatment of idiopathic nephrotic syndrome (INS). The pathogenesis of INS remains unknown, but evidence points toward an immunological basis of the disease. Recently, LMS has been shown to increase the relapse-free survival in INS patients. While LMS has been hypothesized to exert an immunomodulatory effect, its mechanism of action remains unknown. Here, we show that LMS decreased activation and proliferation of human T cells. T-cell activation-associated cytokines such as IL-2, TNF-α, and IFN-γ were reduced upon LMS treatment, whereas IL-4 and IL-13 were increased. Gene expression profiling confirmed that the suppressive effects of LMS as genes involved in cell cycle progression were downregulated. Furthermore, genes associated with p53 activation were upregulated by LMS. In agreement, LMS treatment resulted in p53 phosphorylation and increased expression of the p53 target gene FAS. Accordingly, LMS sensitized activated T cells for Fas-mediated apoptosis. LMS treatment resulted in a mid-S phase cell cycle arrest accompanied by γH2AX-foci formation and phosphorylation of CHK1. Our findings indicate that LMS acts as an immunosuppressive drug that directly affects the activation and proliferation of human T cells by induction of DNA damage and the activation of a p53-dependent DNA damage response.

Treatment of idiopathic nephrotic syndrome at onset: a comparison between 8- and 12-week regimens in everyday clinical practice.

Optimal steroid treatment at onset of idiopathic nephrotic syndrome is still debated. The aim of this study was to analyze the clinical outcome at 24months of follow-up in patients admitted to our unit for the first episode of steroid-sensitive nephrotic syndrome comparing two different steroid regimens. We collected data on patients treated from 1992 to 2007 with prednisone according to the International Study on Kidney Diseases in Children 8-week regimen and since 2008 according to the Arbeitsgemeinschaft fur Padiatrische Nephrologie 12-week regimen. The primary outcome was to evaluate cumulative prednisone dosage at 12 and 24months of follow-up in the two groups. As secondary outcomes, we considered mean relapse rate per patient; number of children without relapses at 6, 12, and 24months; and number of patients who developed frequent relapses and steroid-dependent disease. Data were collected on 127 patients. Sixty-one subjects received the 8-week regimen and 66 the 12-week regimen. The mean cumulative prednisone dose at 12 and 24months was not different, and the rate of patients without relapses was lower at 6 and 12months in patients treated with the 8-week course, while no difference was observed at 24months. Despite the limitations of a retrospective study with limited follow-up, our data indicate that switching treatment from a shorter to a longer scheme did not improve the clinical outcome at 24months of observation. A higher resolution version of the Graphical abstract is available as Supplementary information.

RESULTS OF TREATMENT OF CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME AT BAC NINH OBSTETRIC AND CHILDREN'S HOSPITAL

Objectives: describe the clinical characteristics, laboratory findings and evaluate the results of treatment of idiopathic nephrotic syndrome in pediatric patients at Bac Ninh Obstetrics and Children’sHospital. Method: descriptive study. From January 1, 2020 to June 30, 2021.Result: Fiffty two children were recruited into the study sample. Males got involed in this disease more than females with a ratio male to female of 2.05/1 (there were 17 women and 35 men). The meanage was 6,75 years (from 1 to 15 years old), 55,8% of them were under 5 years old. The percentages of severe edema was 7,7%; increased blood pressure was 9.6%; anuria was 19.2%. The average 24-hour proteinuria was 143.46 mg/kg/day; average protein/creatinine ratio was 878.08 mg/mmol. The percentages of patient with good treatment results is 76.9%. Proteinuria, protein/creatinine in urinedecreased significantly after treatment (p<0.05). Blood albumin increased and cholesterol decreased significantly after treatment (p<0.05).Conclusion: Children with idiopathic nephrotic syndrome most were males, young age, severe edema, severe reduction in blood protein and proteinuria. The disease was completely treatable and monitored locally

Treatment of idiopathic nephrotic syndrome with two steroid dosing regimens - one-year observational study.

IntroductionThe aim of the study was to compare the first year of disease in children with idiopathic nephrotic syndrome (INS) treated according to two prednisone dosing regimens: a weight-based schedule (2 mg/kg/24 h in the 1st month, 2 mg/kg/48 h in the 2nd month, with dose tapering during the following 4 months), and a body surface area (BSA)-based schedule (60 mg/m2/24 h in the 1st month, 40 mg/m2/48 h in the 2nd month, with dose tapering during the following 4 months).Material and methodsIn 2 groups of children treated with weight- and BSA-based regimens (20 patients, 3.13 ±1.01 years, treated in 2010-2013 and 20 patients, 5.13 ±2.86 years, treated in 2014-2016) clinical and anthropometrical parameters, number of INS relapses, total prednisone dose (mg/kg/year), and steroid adverse effects were compared during the first year of disease.ResultsChildren treated with the weight-based steroid regimen received a higher total annual prednisone dose (259.06 ±79.54 vs. 185.83 ±72.67 mg/kg/24 h, p = 0.004) and had a shorter (though not significantly) period without prednisone (38.25 ±55.83 vs. 75.90 ±73.06 days, p = 0.062) compared to patients treated with the BSA-based regimen. There was no difference in number of relapses between groups (2.20 ±1.64 vs. 1.60 ±1.67, p = 0.190) but more patients relapsed in the weight-based group (19/20 vs. 13/20, p = 0.044). No differences in Z-score values of height, weight, and body mass index (BMI) were observed. No steroid-related adverse events were noted except for arterial hypertension (4/20 vs. 5/20 patients, p = 1.000).ConclusionsThe BSA-based regimen of prednisone dosing in children with INS reduces exposure to steroids and risk of relapse, as well as increases days off steroids in the first year compared to the weight-based regimen with a high second-month dose.

STEROID-INDUCED GLUCOSE INTOLERANCE IN CHILDREN WITH NEPHROTIC SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOUS

Steroids are the cornerstone in treatment of idiopathic nephrotic syndrome (INS) and systemic lupus erythematosus (SLE). Steroids are used for their anti-inflammatory and immunosuppressive effects. Although, they are known to cause serious adverse effects including glucose intolerance.The mechanisms by which steroid-induced glucose intolerance (SIGI) include: increased gluconeogenesis in the liver, reduced glucose uptake in adipose tissue and skeletal muscle, and induced pancreatic β-cell dysfunction. The exact prevalence of SIGI in patients on chronic steroid therapy is unknown. The prevalence was reported to vary between 0% and 65% and several risk factors for the developing SIGI have been identified. THE AIM OF THIS WORK The aim of this work was to study steroid-induced glucose intolerance in patients with idiopathic nephrotic syndrome and systemic lupus erythematosus on long term steroid treatment and to determine the risk factors associated with development of steroid-induced glucose intolerance.SUBJECTSSubjects were recruited directly from outpatient Pediatric Nephrology Clinic. Sixty children aged from 2 to 18 years were enrolled; including 2 groups: thirty patients with INS and thirty patients with SLE on long-term steroids use for at least 6 months.

Comparative evaluation of the effectiveness of Cyclosporine A and Tacrolimus in the treatment of idiopathic nephrotic syndrome in children

Comparative evaluation of the effectiveness of Cyclosporine A and Tacrolimus in the treatment of idiopathic nephrotic syndrome in children

Trendy w terapii idiopatycznego zespołu nerczycowego u dzieci na podstawie doświadczeń jednego ośrodka

Trendy w terapii idiopatycznego zespołu nerczycowego u dzieci na podstawie doświadczeń jednego ośrodka

Variability of diagnostic criteria and treatment of idiopathic nephrotic syndrome across European countries

The variability in the approach of idiopathic nephrotic syndrome is unexpectedly large and affects treatment of the first flare, strategies in the case of steroid dependency, as well as the definitions of steroid resistance. What is Known: • Steroids and immunosuppressants are the universal treatment of idiopathic nephrotic syndrome. What is New: • The variability of treatments and strategy of treatment in European centers of pediatric nephrology.

The mechanisms of steroid resistance of children's idiopathic nephrotic syndrome

The resistance to steroid remains a major trouble in the treatment of idiopathic nephrotic syndrome, and the mechanisms are complicated.Recent studys have shown that multidrug resistance gene l and P-glycoprotein170, glucocorticoid receptor, renal pathology, gene mutation and complications are all closely related to the resistance to steroid.This review is focused on the mechanisms of steroid resistance of children's idiopathic nephrotic syndrome. Key words: Idiopathic nephrotic syndrome; Children; Steroid resistance

Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome.

Glucocorticosteroids (GCs) are the first-line treatment for idiopathic nephrotic syndrome (NS), but prolonged administration interferes with growth and bone mineralization. We conducted a retrospective study to analyze the long-term impact of prednisone on growth and bone mineral density (BMD) in children with NS. Data from children with NS followed during almost 10 years were analyzed. Height and spine BMD values were converted to Z-scores (standard deviation [SD]). The mean cumulative dose of GCs received was calculated and correlated to patient's growth and spine BMD using linear regression and subgroup analysis. We included 30 patients diagnosed at 3.7 years old (interquartile range (IQR) 2.6-4.8) and followed over 9.8 years (IQR 6.6-11.7). The one half of NS patients was steroid sensitive and one half dependent or resistant. The median cumulative dose of GCs received was 0.27 mg/kg/day (IQR 0.18-0.35). Growth and spine BMD were both negatively associated with the cumulative dose of GCs (P=0.001 and P=0.037, respectively). Final height Z-scores were significantly lower in patients receiving >0.2 mg/kg/day GCs (P=0.001). No difference was observed in spine BMD between subgroups. Increasing doses of GCs were significantly associated with lower height and BMD Z-scores. A significant effect on growth was observed with cutoff doses above 0.2 mg/kg/day.

Is rituximab effective in childhood nephrotic syndrome? Yes and no

The idiopathic nephrotic syndrome (i.e. MCNS and FSGS) in children has been regarded as a disorder of T-cell function. Recent studies, however, also describe abnormalities of B-cell function. This supports the use of B-cell modulating treatment for idiopathic nephrotic syndrome (INS), especially rituximab, which has been used in other glomerular disorders as well. Many studies indicate that rituximab is effective in steroid-sensitive and -dependent nephrotic syndrome, by either inducing long-term remission or reducing relapses. In most series, children with primary (and recurrent) focal segmental glomerulosclerosis (FSGS) do not respond as well. The exact mechanisms of action of rituximab (as well as those of the other treatment options) in INS are as yet unclear. In addition to hosting mechanisms a direct stabilizing effect on the podocyte may also be of relevance, especially in FSGS. Although results are encouraging especially in steroid-sensitive patients, further studies on the clinical use of rituximab and the short- and long-term immunological effects and side-effects are necessary.

Role of Therapeutic Apheresis in the Treatment of Idiopathic Nephrotic Syndrome

Idiopathic NS (INS) is characterized by diffuse foot process effacement on electron microscopy and minimal changes (minimal change nephropathy [MCN]), or focal segmental glomerular sclerosis (FSGS) on optical microscopy. MCN is the most common form of INS in children and is sensitive to corticosteroid therapy in almost cases. FSGS is more common in adult patients and has a less favourable course. Most of drug resistant patients develop terminal renal failure in 6–8 years. Moreover, FSGS reappears in many cases after renal transplantation. Genetic or secondary forms of INS have been identified and their response to therapy is unpredictable, whereas the recurrent forms in transplanted kidney are considered a more omogeneous group. Sera from patients with FSGS may contain some proteinuric or permeability factors (PFs), which have been partially identified. Corticosteroids and immunosuppressive drugs are the mainstay of the standard therapy. In steroid resistant cases, new therapeutic strategies directed agai...

Proteomic Profiling Identifies Haptoglobin as a Potential Serum Biomarker for Steroid-Resistant Nephrotic Syndrome

Background: Long-term outcomes for patients with adult idiopathic nephrotic syndrome correlate closely with steroid responsiveness. The aim of this prospective study was to evaluate the difference in serum proteomes between steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) patients and identify potential biomarkers for the prediction of SRNS. Methods: We performed a gel-based proteomic study of serum obtained from SRNS and SSNS patients and healthy controls at the time of presentation (n = 6 for each group). Proteins from the serum samples were separated using 2-D electrophoresis, digested in-gel and subjected to MALDI-TOF-MS/MS analysis. Further validation was performed utilizing Western blot and ELISA. The sensitivities and specificities of the candidate proteins for predicting SRNS were determined using receiver operating characteristic curves. Results: Thirteen differentially expressed proteins were identified as haptoglobin (Hp) with different isoelectric points and molecular weights. Western blot and ELISA analysis of samples from 146 subjects (healthy controls = 52, SSNS = 54, SRNS = 40) showed a markedly increased level of Hp in the serum, but not urine, of SRNS compared to SSNS patients. The optimal serum cutoff level of Hp was set at ≥1,279 µg/ml using the receiver operating characteristic curve. The sensitivity and specificity for predicting SRNS were 85.0 and 96.3%, respectively. Conclusions: This study provides a novel overview of the difference in serum proteomes of SSNS and SRNS patients. Serum Hp may be a useful predictive biomarker for steroid therapy efficacy in the treatment of idiopathic nephrotic syndrome.

Efficacy and Safety of Treatment with Rituximab for Difficult Steroid-Resistant and -Dependent Nephrotic Syndrome

The treatment of idiopathic nephrotic syndrome is often complicated by a refractory and relapsing course, with risk of drug toxicity and progressive renal failure. We report the efficacy and safety of rituximab in patients with steroid-resistant (SRNS) and steroid-dependent nephrotic syndrome (SDNS) refractory to standard therapy. This was a cohort study in academic, tertiary care centers in India and the United States. Patients with SRNS or SDNS, not responding to medications or showing calcineurin inhibitor toxicity, treated with two to four doses of intravenous rituximab, and followed ≥12 months were included. Remission was termed as complete, partial, or no response. Thirty-three patients with SRNS (24 initial, 9 late resistance) and 24 with SDNS, with mean ages of 12.7 ± 9.1 and 11.7 ± 2.9 years, respectively, were included. Six months after rituximab therapy, 9 (27.2%) patients with SRNS showed complete remission, 7 (21.2%) had partial remission, and 17 (51.5%) had no response. At 21.5 ± 11.5 months, remission was sustained in 15 (complete: 7, partial: 8) patients. Of 24 patients with SDNS, remission was sustained in 20 (83.3%) at 12 months and in 17 (71%) at follow-up of 16.8 ± 5.9 months. The mean difference in relapses before and 12 months after treatment with rituximab was 3.9 episodes/patient per year. Therapy with rituximab was safe and effective in inducing and maintaining remission in a significant proportion of patients with difficult SRNS and SDNS.

Effect of Cyclosporine Therapy With Low Doses of Corticosteroids on Idiopathic Nephrotic Syndrome

Cyclosporine (CyA) has an immunosuppressive effect that might suggest a therapeutic role in idiopathic glomerular conditions. We focused on the optimization of CyA treatment control in patients with idiopathic nephrotic syndrome by using trough-level CyA measurements (C0) and the 2-h postdose levels (C2). Twenty-two patients (14 male, 8 female) with idiopathic nephrotic syndrome and the mean age of 51 +/- 18 months (mean [M] +/- standard deviation [SD]) were enrolled in our study during a period of 10 months (range: 3-18 months). All of the patients received CyA (2-3 mg/kg) in combination with methylprednisolone. In the present study protocol CyA concentrations (C0, C2), renal function, lipid profile, and degree of proteinuria were determined. The mean proteinuria of our patients before treatment was 11 972 +/- 7953 mg/24 H (+/-SD) and the mean creatinine level (Cr) was 0.99 +/- 0.37 mg/dL (+/-SD). Proteinuria decreased significantly already from the first month of therapy with CyA to 3578 +/- 2470 mg/24 H (M+/- SD), and during the whole study period this reduction was significant (0.56 +/- 0.37 gr/24 H (M +/- SD), P < 0.05). At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). The blood levels of C0 were 135.10 +/- 97.36 ng/mL (M +/- SD) and the blood levels of C2 were 725 +/- 256 ng/mL (M +/- SD) at the first month of therapy. At the same time renal function preserved, 1.09 +/- 0.48 mg/dL (M +/- SD). Total cholesterol levels reduced significantly during study period (276.89 +/- 45.57 to 200.67 +/- 40.27 mg/dL [M +/- SD]). The mean number of antihypertensive medication remained the same. The whole therapeutic protocol did not provoke any kind of side effects and CyA was quite tolerated by our patients. Treatment of idiopathic nephrotic syndrome with low doses of CyA with methylprednisolone leads to remission of proteinuria without deterioration of renal function. Blood levels of C0 for monitoring and treatment of nephrotic syndrome agrees with recent literature, while our study focus on establishing the proper levels of C2 for the treatment of nephrotic syndrome. The efficacy of CyA is combined with safety and tolerance.

A comparison of a standard-dose prednisone regimen and mycophenolate mofetil combined with a lower prednisone dose in chinese adults with idiopathic nephrotic syndrome who were carriers of hepatitis B surface antigen: A prospective cohort study

Background: When receiving immunosuppressive therapy, patients with idiopathic nephrotic syndrome who are also carriers of hepatitis B virus (HBV) surface antigen (HBsAg) are at risk for reactivation of HBV.Objective: This study compared the effectiveness and tolerability of a standard-dose prednisone regimen with those of the combination of mycophenolate mofetil (MMF) and a lower prednisone dose for the treatment of idiopathic nephrotic syndrome characterized by minimal-change nephropathy or slight mesangial proliferative glomerulonephritis in Chinese adults who were also carriers of HBsAg, a combination here termed MSNS-HBV.Methods: This was a prospective, open-label cohort study in Chinese adults with MSNS-HBV. Patients were self-assigned to 1 of 2 treatment groups: the standard prednisone regimen of 1 mg/kg daily or oral MMF 0.5 to 1.0 g BID combined with the lower pred-nisone dose of 0.5 mg/kg daily. The planned duration of treatment was 36 weeks, with an additional 60 weeks of follow-up. The primary outcome measures were rates of complete remission of idiopathic nephrotic syndrome (a decrease in daily proteinuria to within the normal range [<0.3 g]) and rates of HBV reactivation (detectable serum HBV DNA). Secondary outcome measures included relapse rates (>1+ albuminuria on dipstick urinalysis on 3 consecutive days), alanine ami-notransferase (ALT) elevations (>50 U/L), use of la-mivudine 100 mg/d (added if HBV DNA titers reached ≥105 copies/mL), and adverse effects.Results: The intent-to-treat population included 41 patients (22 prednisone, 19 MMF). In patients who completed the study, rates of complete remission after 24 weeks of treatment were 78.9% (15/19) in the prednisone group and 76.5% (13/17) in the MMF group; 2 and 3 patients in the respective groups had a partial remission, and 2 and 1 patient had no response. HBV reactivation occurred in 63.6% (14/22) and 36.8% (7/19) of patients (P = 0.047). The only significant difference in the study was in the probability of HBV reactivation between groups (P = 0.043, log-rank test). During follow-up, at least 1 relapse occurred in 46.7% (7/15) and 30.8% (4/13) of patients. Elevations in ALT were observed in 36.4% (8/22) and 26.3% (5/19) of patients, and the addition of lamivu-dine was required in 40.9% (9/22) and 21.1% (4/19) of patients. The most frequent adverse effects in both groups were infections (27.3% and 26.3%), followed by gastrointestinal symptoms (13.6% and 21.1%). Two MMF patients developed leukopenia. One patient in the prednisone group discontinued treatment because of severe hepatitis, and 1 patient in the MMF group discontinued because of severe pulmonary infection.Conclusions: Among the adult Chinese patients with MSNS-HBV who completed this study, there were no significant differences in remission rates of idiopathic nephrotic syndrome between the standard prednisone regimen and the combination of MMF and a reduced prednisone dose. Rates of HBV reactivation, however, were significantly lower in the combination-therapy group.

Tacrolimus in the treatment of idiopathic nephrotic syndrome

The immunosuppressant tacrolimus (FK-506) is a calcineurin inhibitor with a widespread use for the prevention of graft rejection in transplantation medicine. Tacrolimus inhibits the activation of an essential transcription factor for the transcription of cytokine genes in T cells leading to a decreased production of cytokines such as IL-2 and IFN-γ. As T-cell activation plays a crucial role in the pathogenesis of inflammatory glomerular diseases, there is an increasing number of reports on the use of tacrolimus in nephrotic syndrome. In idiopathic nephrotic syndrome, corticosteroid treatment constitutes the first-line therapy to achieve remission. In the case of steroid resistance or steroid dependence, alternative immunosuppressive strategies are needed. Cyclophosphamide and ciclosporin are well-established drugs in this condition. The present article reviews the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome.