Development and validation of a diagnostic nomogram to evaluate tubular atrophy/interstitial fibrosis of IgA nephropathy.

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.

Association between geriatric nutritional risk index and pathological phenotypes of IgA nephropathy.

Background: IgA nephropathy (IgAN) is an immune disease related to oxidative stress and inflammation. It is the most common type of glomerulonephritis in the world and is the cause of chronic kidney disease and end-stage renal disease (ESRD). The Geriatric Nutritional Risk Index (GNRI) is a practical and uncomplicated method to assess the risk of morbidity and mortality, but its ability to assess IgAN is still unclear. Here, we evaluated the association between the GNRI and clinical and histologic findings of IgAN. Methods: In a cross-sectional study, we included 348 biopsy-verified IgAN patients. The Oxford classification was used to analyze the pathological characteristics of the included patients. Based on previous studies, the participants were divided into two groups using a cutoff value of 92. Differences in clinicopathological indices between the two groups were compared. The correlation between the GNRI and the indicators was evaluated by using a bivariate correlation analysis. A binary logistic regression analysis was conducted to determine the factors associated with the crescent lesions in IgAN. Results: In this study, 138 out of 348 patients (39.7%) had low GNRI scores (GNRI < 92). Patients in the low GNRI group tended to have a significantly lower body mass index; lower hemoglobin, serum albumin, serum IgG, and serum C3 levels; and higher 24-h proteinuria. The proportions of females, Oxford M1 and Oxford C1/2 were higher in the low GNRI group. The GNRI was positively correlated with body mass index (r = 0.57, P < 0.001), hemoglobin (r = 0.35, P < 0.001), serum albumin (r = 0.83, P < 0.001), serum IgG (r = 0.32, P < 0.001), and serum C3 (r = 0.26, P < 0.001) and negatively correlated with 24-h proteinuria (r = -0.36, P < 0.001) and the proportion of crescents (r = -0.24, P < 0.001). The GNRI scores and serum IgG levels were considered independent factors influencing the crescent lesions in IgAN. Conclusions: The GNRI can reflect the severity of clinical and histologic phenotypes in IgAN patients. Lower GNRI and serum IgG levels may suggest an increased risk of crescent lesions and are potential markers for disease monitoring in IgAN.

Corrigendum: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

[This corrects the article DOI: 10.3389/fimmu.2022.978315.].

Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

Background: Renin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN. Methods: We included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients. Results: After screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN. Conclusions: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.

Association of fetuin-A levels and left ventricular diastolic dysfunction in patients on haemodialysis.

OBJECTIVE: To identify the relationship between serum fetuin-A levels and left ventricular diastolic dysfunction (LVDD) among maintenance haemodialysis patients. METHODS: In a cross-sectional study, 75 dialysis patients with end-stage renal disease (ESRD) were recruited, and fetuin-A levels were detected using an enzyme-linked immunosorbent assay (ELISA). Echocardiography measurements were recorded according to the recommendations of the American Society of Echocardiography. The ratio of early diastolic transmitral inflow velocity (E) to early diastolic annular velocity (E') was measured using tissue Doppler imaging and E/E' > 15 was defined as diastolic dysfunction. The association of serum fetuin-A concentrations with echocardiographic parameters was analysed by calculating the bivariate linear correlation. A binary logistic regression analysis was conducted to determine the variables associated with LVDD. RESULTS: Compared to patients without diastolic dysfunction, patients with diastolic dysfunction were older, a higher percentage had a history of coronary artery disease, and presented with a high systolic pressure, high parathyroid hormone level, high N-terminal pro-brain natriuretic peptide (NT-proBNP) level, high LV mass index, high left atrium diameter, and low serum creatinine and fetuin-A levels. Serum fetuin-A levels showed a negative correlation with E/E' (r = - 0.299, P = 0.009). Fetuin-A levels were considered an independent predictor of diastolic dysfunction. CONCLUSION: A decrease in the serum fetuin-A level is associated with an increased risk of LVDD in patients on haemodialysis.