Predict Steroid Responsiveness Research Articles

The utility of biomarkers to predict steroid response in idiopathic nephrotic syndrome

Objective: The most common form of nephrotic syndrome (NS) is minimal change disease (MCD) in children and focal segmental glomerulosclerosis (FSGS) following it. As, it is important to predict corticosteroid (CS) response at the beginning of the disease, we aimed to evaluate the efficacy of some biomarkers in terms of predicting steroid response in patients with NS. Patients and Methods: Twenty patients who met the inclusion criteria for the study were divided into 3 groups and 6 healthy control participants were included in the analysis as the 4th group. Group-1 included 10 patients at the first episode of idiopathic NS (INS), group-2 included the same 10 patients in remission, group-3 included 10 patients with steroid resistant NS (SRNS) diagnosed as FSGS by renal biopsy, and group-4 included six healthy children as controls. Urinary and serum cluster of differentiation (CD) CD80, IL-17, IL-23, IL-10, TGF-β, CD86, CD28, CTLA-4 levels were measured for all groups. Results: Urinary CD80 level in INS-relapse group was significantly higher than the levels of the INS-remission, FSGS and control groups (p

Peripheral Blood Cell DNA Methylation Can Predict Steroid Response in Nephrotic Syndrome

Peripheral Blood Cell DNA Methylation Can Predict Steroid Response in Nephrotic Syndrome

#2045 Epigenetic data can predict initial treatment response in nephrotic syndrome

Abstract Background and Aims The majority of children with idiopathic nephrotic syndrome (INS) and adults with Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) receive glucocorticoid treatment at diagnosis. Only those with a high likelihood of having monogenic disease or a contraindication to steroids might avoid this treatment. About 10% overall will not respond to steroids and we have no reliable way of prospectively identifying these patients. Therefore, some patients will receive a futile treatment which is accompanied by significant side effects. DNA methylation (DNAm) is an epigenetic mechanism meaning that it can induce stable but reversible changes in gene expression without any change in underlying DNA sequence. DNAm has shown great potential as a treatment stratification tool, for example, DNAm data is used in oncology to identify which patients are likely to benefit from alkylating chemotherapy. We investigated whether DNAm can predict initial response to steroids in children and young adults with nephrotic syndrome. Method Three hundred and seventeen patients with INS were selected from the NephroS and NURTuRE cohorts. All patients were diagnosed with INS ≤ 30 years of age and those who underwent a renal biopsy had a histological diagnosis of either FSGS or MCD. Peripheral blood DNAm measurements were generated using the Illumina MethylationEPIC Beadchip (>850, 000 CpG sites). Clinical data was used to label patients by their initial response to steroids (sensitive, n = 156, or resistant, n = 161). Machine learning models were created to predict steroid response from the DNAm data. Models were generated using elastic net following feature filtering, and model hyperparameters were tuned and performance measured within the context of cross validation. To exclude whether cumulative steroid exposure prior to sample collection had impacted our results, the CpG sites in the final model were compared to those identified in a published study examining steroid exposure and DNAm (4). Results The 317 INS patients had a median age at diagnosis of 5 years (IQR 2-10) and a median time between diagnosis and DNAm sample collection of 4 years (IQR 1-10). The steroid resistant group were made up of patients with known monogenic disease (n = 75, 24%) and those without pathogenic variants (n = 86, 27%). Initial response to steroid treatment could be predicted with 65% accuracy and an area under the curve (AUC) of 0.75, (sensitivity 0.65, specificity of 0.66, see Fig. 1) using DNAm levels at 14 CpG sites. There was no overlap between the 14 CpG sites in our prediction model and those that are known to alter with steroid treatment. Conclusion We have demonstrated that peripheral blood cell DNAm profiles are a promising predictor of steroid response in INS. Further work to incorporate genetic data into the prediction models is underway and external validation of the results in a separate cohort of patients is required.

Prothrombin time predicts steroid response in severe alcohol-related hepatitis.

Alcohol-related hepatitis (AH) is the most severe form of acute alcohol-related liver disease. Maddrey's discriminant function ≥32 defines the severe form of AH, which is associated with a high mortality. Steroid therapy represents the main medical treatment that may reduce short-term mortality. Lille score at day 7 assesses the therapeutic response to steroid therapy. At present, no parameters able to predict the response to steroid therapy have been highlighted. The aim of the present study was to evaluate if baseline prothrombin time (BPT) could predict the response to steroid in severe AH (sAH). Patients consecutively admitted in two Italian Liver Units, from 2017 to 2022, suffering from sAH were included. Data were collected prospectively. In order to evaluate if BPT could predict steroid response, we assessed the correlation between BPT using the Lille score at day 7. A total of 52 patients received steroid treatment were enrolled in the study. The response to therapy was assessed by Lille score at day 7. Responders were 34 patients (65%), non-responders 18 patients (34%). BPT significantly predicted the steroid response (p < .001). The likelihood of not responding to the steroid therapy was significantly higher in patients with higher BPT (OR = 2.954). BPT value predicted steroid response in patients with sAH. BPT could quickly identify non-responder patients to steroid therapy, reducing the risk of infections and it could allow the early evaluation for liver transplantation.

Tumor necrosis factor alpha gene polymorphism affects the pattern of idiopathic nephrotic syndrome in Kuwaiti Arab children.

TNF-α is a pro-inflammatory cytokine that has been implicated in many inflammatory diseases, but its association with idiopathic nephrotic syndrome (INS) is poorly understood. This study looked for an association of TNF-α gene polymorphisms with INS, as well as its effect on steroid responsiveness among Kuwaiti Arab children. Genotypes of the TNF-a gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism in 151 INS Kuwaiti Arab patients and 64 age and sex-matched controls. Clinical data of all subjects were reviewed. The heterozygous AG genotype was detected in 8.6% of INS patients compared 23.4% of the controls (p < 0.01). Comparing steroid responsiveness, AA genotype was significantly more common in steroid-sensitive nephrotic syndrome (SSNS) cases than steroid-resistant nephrotic syndrome (SRNS) patients (p = 0.001). However, AG genotype was significantly more common in SRNS patients compared to the SSNS cases (p = 0.001). No difference was found between these two subgroups in the GG genotype frequency. AG genotype of TNF-a gene polymorphisms may be considered a suitable marker for INS disease among Kuwaiti children. Both AA and AG genotypes may be useful in predicting steroid responsiveness among these cases of Arab ethnicity. The findings might open the era for the use of genetic markers in the early treatment of NS.

"Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial." D. Stolz, E. Papakonstantinou, M. Pascarella, et al. Eur Respir J 2023; 62: 2300218.

"Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial." D. Stolz, E. Papakonstantinou, M. Pascarella, et al. Eur Respir J 2023; 62: 2300218.

External Validation of a Urinary Biomarker Risk Score for the Prediction of Steroid Responsiveness in Adults With Nephrotic Syndrome

In idiopathic nephrotic syndrome, response to corticosteroids remains the best indicator of prognosis. Noninvasive markers to predict a patient's response to steroids would allow improved prognostication and a more personalized approach to management. We have previously derived a urinary biomarker risk score which can differentiate steroid sensitive nephrotic syndrome (SSNS) from steroid resistant nephrotic syndrome (SRNS) in children. The goal of this study was to validate this previously derived biomarker risk score in a cohort of steroid-naïve adult patients, to determine whether the panel could be used to predict steroid responsiveness at the time of initial diagnosis. In this external validation study, clinical data, and urinary specimens (obtained before initiation of steroid treatment) from adult patients were used in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. A panel of 5 previously identified and validated urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), vitamin D binding protein (VDBP), Fetuin-A (FetA), Transthyretin (TTR), and alpha-1 acid glycoprotein 2 (AGP2) was measured. A summary risk score for steroid resistance was calculated based on biomarker concentrations. Receiver operating characteristic curves were created for each log-transformed biomarker concentration and for the individual and combined biomarker risk score. The urine biomarker risk score predicted development of steroid resistance, with optimal sensitivity and specificity of 0.74, and area under the receiver operating characteristic curve (AUC) of 0.79 using both absolute and creatinine-corrected concentrations. This study validates the previously derived urinary biomarker risk score to predict steroid resistance in adult patients with nephrotic syndrome at initial diagnosis.

Predicting steroid responsiveness using airway smooth muscle in COPD: a HISTORIC study

Predicting steroid responsiveness using airway smooth muscle in COPD: a HISTORIC study

Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.

Although inhaled corticosteroids (ICS) are highly effective in asthma, they provide significant but modest clinical benefit in COPD. Here, we tested the hypothesis that high bronchial airway smooth muscle (ASMC) area in COPD is associated to ICS responsiveness.In this investigator-initiated and -driven, double-blind, randomised, placebo-controlled trial (HISTORIC), 190 COPD patients, GOLD stage B-D, underwent bronchoscopy with endobronchial biopsy. Patients divided in groups A and B with high ASMC area (HASMC: >20% of the bronchial tissue area) and with low ASMC area (LASMC: ≤20% of the bronchial tissue area), respectively and followed a run-in period of 6 weeks on open-label triple inhaled therapy with aclidinium/formoterol/budesonide (ACL/FOR/BUD:400/12/400 mcg/bid). Subsequently, patients were randomised to receive either ACL/FOR/BUD or ACL/FOR/Placebo and followed for 12 months. The primary end point of the study was the difference in post-bronchodilator FEV1 over 12 months between patients with LASMC and HASMC receiving or not receiving ICS.In patients with LASMC, ACL/FOR/BUD did not significantly improve FEV1 over 12 months, as compared to ACL/FOR/placebo p=0.675. In patients with HASMC, however, ACL/FOR/BUD significantly improved FEV1, as compared to ACL/FOR/placebo p=0.020. Over 12 months, the difference of FEV1 change between the group of ACL/FOR/BUD and the group of ACL/FOR/placebo was 50.6 mL·year-1 within the group of patients with LASMC and 183.0 mL·year-1 within the group of patients with HASMC.COPD patients with ΗASMC respond better to ICS than patients with LASMC, suggesting that this type of histological analysis may predict ICS responsiveness in COPD patients receiving triple therapy.

#2519 THE EFFECT OF TRPC5 AND PALLADIN EXPRESSION ON TREATMENT RESPONSE AND RENAL OUTCOME IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is a disease that is among the primary glomerulopathies and often progresses to chronic renal failure. Despite advances in immunosuppressive therapy for the treatment of glomerular diseases, some FSGS patients are resistant to single or combination immunosuppressive regimens containing; glucocorticoids, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil (MMF), and/or rituximab. FSGS-related nephrotic syndrome, the degree of proteinuria and response to steroid therapy are the most important factors associated with long-term prognosis, independent of histological findings. Failure to respond to immunosuppressive therapy, including corticosteroids, has been evaluated as one of the most important markers of the risk of developing renal failure. Unfortunately, there is no reliable marker that can predict steroid response. One of the earliest manifestations of podocyte damage is cytoskeletal remodeling, known as deletion of foot ridges. It was recently shown that transient receptor potential channel 5 (TRPC5) plays an important role in initiating this process. However, the role of TRPC5 in disease progression is unknown. It is thought that calcium influx caused by sustained TRPC5 activation in the chronic disease setting may lead to calcium toxicity and podocyte death. It is known that the actin regulatory protein palladin, which is highly expressed here, is also highly related to podocyte function and podocytopathies, and plays an important role in the stability of the actin cytoskeleton. The aim of our study was to define the frequency of TRPC5 and palladin renal expressions in podocytes in focal segmental glomerulosclerosis (FSGS) and its relationship with prognosis and treatment response. Method A total of 182 patients were enrolled for baseline clinical and histopathological features and 103 patients with a clinical follow-up for more than 2 years were evaluated for outcomes. Immunohistochemical staining was performed with TRPC5 and palladin antibodies on kidney biopsies and glomerular staining was evaluated. Results Baseline characteristics, and health parameters were similar between TRPC5+/TRPC5− and palladin+/palladin− groups. TRPC5 expression was observed in 69% of the patient biopsies and palladin expression in 73%. We found that TRPC5 and palladin expression was a significant predictor of FSGS severity and poor treatment response (both p&amp;lt;0.05). In addition, TRPC5 expression was significantly associated with the development of end-stage renal disease and ongoing proteinuria. Conclusion The development of proven treatments that delay the progression of FSGS is critical to patient survival. The development of new treatments is possible only by knowing the underlying pathophysiological mechanism of the disease. Podocyte loss is a critical step in the development of irreversible glomerulosclerosis, which causes chronic kidney disease. Therefore, blocking TRPC5 channel and palladin may be an effective treatment strategy, especially in treatment-resistant FSGS patients with positive staining on biopsy. Our study is the first in the literature to show these two antigens in kidney tissue in FSGS and to associate them with disease prognosis. TRPC5 and palladin expression may serve as a biomarker to facilitate diagnosis and choose new treatment regimens of proteinuric kidney diseases in the future.

Machine learning models for predicting steroid-resistant of nephrotic syndrome.

In the absence of effective measures to predict steroid responsiveness, patients with nonhereditary steroid-resistant nephrotic syndrome (SRNS) have a significantly increased risk of progression to end-stage renal disease. In view of the poor outcomes of SRNS, it is urgent to identify the steroid responsiveness of idiopathic nephrotic syndrome (INS) early. To build a prediction model for SRNS, we collected 91 subjects; 57 of them had steroid-sensitive nephrotic syndrome, and the others had SRNS. For each subject, 87 clinical variables were measured. In general, only a small part of these variables is informative to SRNS. Thus, we proposed a new variable selection framework including a penalized regression approach (named MLR+TLP) to select variables having a linear effect on the SRNS and a nonparametric screening method (MAC) to select variables having a nonlinear marginal (joint) effect on the SRNS. Thereafter, considering the correlation between selected clinical variables, we used a stepwise method to build our final model for predicting SRNS. In addition, a statistical testing procedure is proposed to test the overfitting of the proposed model. Twenty-six clinical variables were selected to be informative to SRNS, and an SVM model was built to predict SRNS with a leave-one-out cross-validation (LOO-CV) accuracy of 95.2% (overfitting p value<0.005). To make the model more useful, we incorporate prior medical information into the model and consider the correlation between selected variables. Then, a reduced SVM model including only eight clinical variables (erythrocyte sedimentation rate, urine occult blood, percentage of neutrophils, immunoglobulin A, cholesterol, vinculin autoantibody, aspartate aminotransferase, and prolonged prothrombin time) was built to have a LOO-CV accuracy of 92.8% (overfitting p value<0.005). The validation cohort showed that the reduced model obtained an accuracy of 94.0% (overfitting p value<0.005), with a sensitivity of 90.0% and a specificity of 96.7%. Notably, vinculin autoantibody is the only podocyte autoantibody included in this model. It is linearly related to steroid responsiveness. Finally, our model is freely available as a user-friendly web tool at https://datalinkx.shinyapps.io/srns/. The SRNS prediction model constructed in this study comprehensively and objectively evaluates the internal conditions and disease status of INS patients and will provide scientific guidance for selecting treatment methods for children with nonhereditary SRNS.

A new parameter predicting steroid response in idiopathic IgA nephropathy: a pilot study of pan-immune inflammation value.

In this pilot study, we aimed at investigating the predictive power of pan-immune inflammation value (PIV) on response rates at 6 months in idiopathic IgA nephropathy (IgAN) patients who started steroids. The study was conducted with patients diagnosed with idiopathic IgAN and treated with 3-6 months of conservative treatment and steroid therapy started because proteinuria was above 1 g/day. Patients with proteinuria lower than 0.3 g/day, no macroscopic hematuria, and no hematuria detected in 3 consecutive urinalyses for 6 months were considered to be patients in remission. PIV was calculated by [neutrophil count (103 µL)*platelet count (103 µL)*monocyte count (103 µL)]/lymphocyte count (103 µL)]. Patients were compared according to their remission status in terms of PIV. The mean PIV was significantly higher in patients in the non-remission group than in patients in the remission group (1,869.2±1,781.9 to 574.1±364.5, respectively). The best cut-off for PIV was 752.6 to predict non-remission with a 75% sensitivity and 71.4% specificity. Our study showed that PIV is a reliable marker for predicting steroid response at the 6th month in patients with idiopathic IgAN.

Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.

Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response

ObjectivesWe aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission.DesignOutcomes of 131...

Cochlear implantation in systemic autoimmune disease.

Autoimmune inner ear disease (AIED) is a rare, but likely underrecognized cause of hearing loss. However, hearing loss is common in systemic autoimmune disease and it is important for the clinician to be familiar with the spectrum of disease. In this article, we will review the developments in diagnosis and management of AIED, with a focus on the outcomes and potential pitfalls of cochlear implantation. Hearing loss in AIED tends to be progressive and bilateral, but up to 40% can present as sudden hearing loss and one-third can present unilaterally. HSP-70 serology may help with diagnosis and may predict steroid response. Cochlear implantation provides excellent hearing and quality of life outcomes in patients deafened by AIED. Intracochlear fibrosis/ossification is found intraoperatively in the majority (54%) of patients undergoing cochlear implantation. A large percentage (32%) of patients has fluctuating impedances postimplantation, which may interfere with implant performance and mapping. Diagnosis of AIED is largely clinical, and a strong index of suspicion is required. Multidisciplinary care is crucial for optimal management. Cochlear implant outcomes are generally excellent, but the clinician needs to be cognizant of the pitfalls of encountering intracochlear fibrosis intraoperatively and likelihood of implant performance fluctuation related to ongoing inflammation in the cochlea.

The value of fractional exhaled nitric oxide in occupational diseases – a systematic review

Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of respiratory tract inflammation, originally designated to identify eosinophilic airway inflammation and to predict steroid response. The main field of application of this biomarker is asthma, but FeNO has also been used for other allergic and non-allergic pulmonary disorders such as chronic obstructive pulmonary disease, hypersensitivity pneumonitis and interstitial lung disease. A substantial part of respiratory diseases are related to work, and FeNO, a safe and easy measure to conduct, is a potential valid examination in an occupational setting.This systematic review assesses the value of measuring FeNO related to three types of airborne exposures: allergens, irritants, and respiratory particles inhaled during occupational activities. The review covers results from longitudinal and observational clinical studies, and highlights the added value of this biomarker in monitoring effects of exposure and in the diagnostic criteria of occupational diseases. This review also covers the possible significance of FeNO as an indicator of the efficacy of interventions to prevent work-related respiratory diseases.Initially, 246 articles were identified in PUBMED and SCOPUS. Duplicates and articles which covered results from the general population, symptoms (not disease) related to work, non-occupational diseases, and case reports were excluded. Finally, 39 articles contributed to this review, which led to the following conclusions:a) For occupational asthma there is no consensus on the significant value of FeNO for diagnosis, or on the magnitude of change needed after specific inhalation test or occupational exposure at the workplace. There is some consensus for the optimal time to measure FeNO after exposure, mainly after 24 h, and FeNO proved to be more sensitive than spirometry in measuring the result of an intervention. b) For other occupational obstructive respiratory diseases, current data suggests performing the measurement after the work shift. c) For interstitial lung disease, the evaluation of the alveolar component of NO is probably the most suitable.

Biomarkers Predicting Treatment-Response in Nephrotic Syndrome of Children: A Systematic Review

Purpose: Nephrotic syndrome (NS) is the most common form of glomerulopathy in children. Most pediatric patients respond to glucocorticosteroid treatment (steroid-sensitive NS, SSNS), while approximately 10–15% will remain unresponsive or later become steroid-resistant. There has been a long-standing effort to find biomarkers that may predict steroid responsiveness.Methods: We systematically reviewed current studies which investigated clinically relevant biomarkers for predicting steroid responsiveness in pediatric NS. We performed a PubMed and EMBASE search to identify eligible articles. We collected data on urinary markers, blood/serum markers (including cellular phenotypes and mRNA expression), genotypes and HLA allele frequency.Results: A total of 659 articles were identified following electronic and manual searches. After reviewing the titles, abstracts, and full texts, 72 eligible articles were finally included. Vitamin D-binding protein (VDBP) seemed to be significantly elevated in SRNS than in SSNS, in both serum and urine specimen, although further validation is required.Conclusions: The present paper narratively illustrates current understandings of potential biomarkers that may help predict steroid responsiveness. Further investigation and collaboration involving a larger number of patients are necessary.

Phenotypes of B-Lymphocytes as a Predictor of Steroid Response in Idiopathic Nephrotic Syndrome.

Introduction: The pathogenesis of Idiopathic nephrotic syndrome (INS) is not clear, where the role of B-cells is not yet illustrated. Aim of the study: To evaluate B- cells subsets as a predictor of steroid therapy sensitivity among INS at initial onset. Methods: 45 children with idiopathic nephrotic syndrome were recruited in a follow- up study, patients were divided into steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) groups based on their sensitivities to steroids. Venous blood samples were drawn from all children for assessment of memory B- cell population before and after one year of steroid therapy. Results: We found statistically significant relation between steroid response and total memory CD19+ CD27+B cell at disease onset where it was higher in SSNS group. Our results showed The best cut-off of total CD19+ B cells in predicting steroid response was ≥32.7 with an area under curve (AUC) of 0.445, a sensitivity of 43.9%, a specificity of 50%, a positive predictive value (PPV) of 90%, a negative predictive value (NPV) of 8% and an accuracy of 44.4% (p>0.05) We also found that The best cut-off of CD19+ CD 27+ total memory B cells in predicting steroid response was ≥32 with an AUC of 0.817, a sensitivity of 78%, a specificity of 75%, a PPV of 97%, a NPV of 25% and an accuracy of 77.8% (p < 0.05). Conclusion: CD19+ CD 27+ total memory B cells could help in predicting steroid response among INS patients with a cut-off of total CD 19+B cells above 32.7 and PPV of 90% , a cut-off above 32 in CD19+ CD +27 total memory cells and PPV 97%.

New risk score for predicting steroid resistance in patients with focal segmental glomerulosclerosis or minimal change disease

BackgroundGlucocorticosteroid is used for patients with primary nephrotic syndrome. This study aims to identify and validate that biomarkers can be used to predict steroid resistance.MethodsOur study contained two stages, discovery and validation stage. In discovery stage, we enrolled 51 minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) patients treated with full dose steroid. Five urinary biomarkers including β2-microglobulin (β2-MG) and α1-microglobulin (α1-MG) were tested and candidates’ biomarkers were selected based on their associations with steroid response. In validation stage, candidates’ biomarkers were validated in two prospectively enrolled cohorts. Validation cohort A included 157 FSGS/MCD patients. Validation cohort B included 59 membranous nephropathy (MN) patients. Patients were classified into response group (RG) or non-response group (NRG) based on their responses to steroid treatment.ResultsIn discovery stage, higher urinary β2-MG was independently associated with response to corticosteroid treatment in MCD/FSGS patients [OR = 1.89, 95% CI 1.02–3.53] after adjusted by age and gender. In validation cohort A, patients in NRG had a significant higher urinary β2-MG [Ln (β2-MG/uCr): 4.6 ± 1.7 vs 3.2 ± 1.5] compared to patients in RG. We then developed a 3-variable risk score in predicting steroid resistance in FSGS/MCD patients based on the best predictive model including Ln(β2-MG/uCr) [OR = 1.76, 95% CI 1.30–2.37], age [OR = 1.005, 95% CI 0.98–1.03] and pathology [MCD vs FSGS, OR = 0.20, 95% CI 0.09–0.46]. The area under the ROC curves of the risk score in predicting steroid response was 0.80 (95% CI 0.65–0.85). However, no such association was found in MN patients.ConclusionsOur study identified a 3-variable risk score in predicting steroid resistance in patients with FSGS or MCD.

Steroid Responsiveness in Duchenne Muscular Dystrophy - Predictive Value of Epigenetic Regulator Histone Deacetylase 2.

To find the role of an epigenetic regulator histone deacetylase (HDAC-2) in predicting steroid responsiveness in patients with Duchenne muscular dystrophy (DMD). Peripheral blood mononuclear cells were isolated from three milliliters of venous blood sample of patients with DMD for estimation of HDAC-2 levels. The patients were then given prednisolone at 0.75mg/kg/d and followed up for response. Improvement in muscle power and timed function tests were evaluated 2 monthly for 6 mo. Side- effects of steroids were also noted. HDAC-2 values showed a linear correlation with improvement in muscle power at 6 mo as reflected in direct assessment and in various functional tests. When ≥3 point change from baseline was considered in power of various muscle groups at 6 mo as cut off to distinguish good responders (GR) from poor responders (PR) of steroid, a HDAC-2 value of ≥4.40 seemed to be 92.6% sensitive and 100% specific to distinguish GRs. The degree of improvement in power and various timed function tests at 6 mo could be predicted from the HDAC-2 value of the individual patient recorded at baseline. HDAC-2 levels at baseline might be a good biomarker for predicting steroid response in patients with DMD.