Background: Insulin-like growth factor 1 (IGF-1) plays a vital role in the attainment and maintenance of bone mass throughout life and is closely related to the stature of children. 25-Hydroxyvitamin D (25-OHD) is an intermediate of vitamin D (Vit D) metabolism and a key indicator of Vit D nutritional status. Multiple studies have revealed that IGF-1 levels undergo a non-significant increase after Vit D supplementation. Here, we analyzed the causal and reverse causal relationships between 25-OHD and IGF-1 levels using Mendelian randomization (MR).Methods: Two-sample MR was used to estimate an unconfounded bidirectional causal relationship between the level of IGF-1 and those of Vit D and 25-OHD. Single nucleotide polymorphisms (SNPs) were filtered from genome-wide association studies (GWAS) after a comprehensive search of the Integrative Epidemiology Unit GWAS database. Several MR methods were employed, including inverse-variance weighted (IVW) method, and a sensitivity analysis was undertaken to detect whether pleiotropy or heterogeneity biased the MR results.Results: Genetically predicted IGF-1 was found to have a causal association with Vit D and serum 25-OHD levels, where Vit D and serum 25-OHD levels increased with increasing IGF-1 concentrations (Vit D: IVW β:0.021, 95% CI: 0.005–0.036, p = 7.74 × 10^–3; 25-OHD: IVW β: 0.041, 95% CI: 0.026–0.057, p = 2.50 × 10^–7). A reverse causal effect was also found, indicating Vit D and serum 25-OHD have a positive causal relationship with IGF-1 (Vit D: IVW β:0.182, 95% CI: 0.061–0.305, p = 3.25 × 10^–3; 25-OHD: IVW β: 0.057, 95% CI = 0.017–0.096, p = 4.73 × 10^–3). The sensitivity analysis showed that horizontal pleiotropy was unlikely to bias the causality in this study (MR-Egger: Vit D intercept p = 5.1 × 10^–5, 25-OHD intercept p = 6.4 × 10^–4 in forward analysis; Vit D intercept p = 6.6 × 10^–4, 25-OHD intercept p = 1.9 × 10^–3 in reverse analysis), and a leave-one-out analysis did not identify evidence of bias in the results.Conclusion: The results of the MR analysis provide evidence that IGF-1 has positive causal and reverse causal relationships with Vit D and serum 25-OHD, respectively, in European populations. Our findings also provide guidance for the prevention and treatment of short stature and other related diseases.

Objective: This study aims to investigate the predictive value of early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for relapse and adverse prognosis within one year in children diagnosed with steroid-sensitive nephrotic syndrome (SSNS).Methods: This study included a total of 145 pediatric patients diagnosed with steroid-sensitive nephrotic syndrome (SSNS) between January 2016 and December 2021. We collected early neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels, along with relevant clinical data, and conducted a one-year follow-up of the patients. Based on the follow-up outcomes, the patients were categorized into two groups: those who experienced a relapse and those who did not. We assessed the diagnostic and predictive value of NLR and CRP for relapse within one year using receiver operating characteristic (ROC) curve analysis and the Cox proportional hazards regression model.Results: After an average follow-up period of one year, 95 patients (65.52%) experienced relapse, while 50 patients (34.48%) did not. Significant differences were noted between the relapse and non-relapse groups regarding neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), 24-hour urinary protein levels, age at onset, and parental education level (P < 0.05). Cox proportional hazards regression analysis identified age at onset, NLR, CRP, and 24-hour urinary protein levels as significant risk factors for relapse in patients with steroid-sensitive nephrotic syndrome (SSNS). Receiver operating characteristic (ROC) curve analysis for the combined prediction of relapse using NLR, CRP, and 24-hour urinary protein levels demonstrated good predictive value, with an area under the curve (AUC) of 0.858 (95% CI: 0.80–0.916, P < 0.001). Kaplan-Meier survival analysis indicated that patients with elevated NLR (≥ 2.90) and CRP (≥ 25.30) exhibited the highest relapse rates and shorter survival times. Further Cox proportional hazards analysis revealed that children in the high NLR and high CRP groups were at an increased risk of relapse, rehospitalization, infection, prolonged cumulative steroid use, renal insufficiency, secondary hypertension, and other adverse outcomes within one year.Conclusion: Early levels of Neutrophil-to-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) demonstrate significant predictive value for relapse and adverse prognosis within one year in children with Steroid-Sensitive Nephrotic Syndrome (SSNS). These markers can serve as effective tools for auxiliary clinical assessment.