Abstract
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.
Highlights
Glucocorticosteroid is used for patients with primary nephrotic syndrome
We found that 42.3% focal segmental glomerulosclerosis (FSGS) patients presented with steroid resistance, higher than minimal change disease (MCD) patients (21.4%)
Renal outcome defined as no response to therapy β2-microglobulin; uCr: urinary creatinine a Adjusted by age, gender and clinical parameters b Adjusted by age, gender and pathological parameters c Adjusted by age, gender, clinical parameters and pathological parameters *P < 0.05, #P < 0.01 stage, we found that baseline urinary β2-MG significantly increased in FSGS and MCD patients in the steroid resistant group versus those in the steroid sensitive group
Summary
Glucocorticosteroid is used for patients with primary nephrotic syndrome. This study aims to identify and validate that biomarkers can be used to predict steroid resistance. Primary glomerulonephritis including primary nephrotic syndrome (PNS) is the most common cause of end stage renal disease (PG) in China. A significant proportion of these patients show poor responses to the medication. Severe side effects might occur such as infection, metabolic disturbance or osteoporosis [5, 6]. Various risk factors were found to be associated with steroid resistance, including age, abnormal expression of glucocorticoid receptor, mutations of podocyte-related genes, pathological types, abnormal lipid metabolism or immune factors [7]. Given the drawbacks mentioned above, predicting patients’ response before steroid treatment can be very useful. There is no clinically applicable method to achieve this goal as of
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