Advances in biomarkers of IgA nephropathy.

BACKGROUND: Renal biopsy plays an important role in diagnosis of renal disease, especially in nephrotic syndrome. IgA nephropathy had been the most common glomerular disease in the whole world. However, there were not many reports about the epidemiological incidence and causes of renal disease in Taiwan.METHODS: We performed a single-center, retrospective analysis of patients with renal disease that was documented by precutaneous renal biopsy from October 2000 to December 2010. Demographic data (age, gender), laboratory investigations such as serum urea, serum creatinine, proteinuria, haematuria, 24-hour urinary protein, and creatinine clearance, and clinical diagnosis were collected for analysis.RESULTS: There were 444 native kidney biopsies performed, 238 males (53.6%) and 206 females (46.7%). The average age of patients was 47.6 years. The most common clinical presentation as an indication for renal biopsy was nephrotic syndrome (52%). Membranous nephropathy (17.5%) was the most common glomerular disease and the most frequent cause (29.8%) of nephrotic syndrome. Primary glomerular disease accounted for 55% of all biopsies and membranous nephropathy was the most frequent cause (31.7%) of the primary glomerular disease. Lupus nephritis was the most frequent secondary glomeurlonephritis (53.21%).CONCLUSIONS: Instead of IgA nephropathy, membranous nephropathy was the most common primary glomerular disease and lupus nephritis was the most common secondary glomerulonephritis in our analysis. The high prevalence of membranous nephropathy could be due to older age and higher incidence of patients with nephrotic syndrome in our database.

BackgroundThe worldwide incidence of renal disease diagnosed by a kidney biopsy varies with age, race, sex, and region. Owing to a lack of studies and limited research resources for this disease in Korea, we investigated renal disease patterns by analyzing data from kidney biopsies performed over 13 years in a university-based teaching hospital in Korea.MethodsAmong 2,053 kidney biopsies performed from 2001 to 2013 at Kyungpook National University Hospital, 1,924 were retrospectively analyzed for histopathologic, demographic, and clinical data as well as laboratory results.ResultsAmong the 1,924 studied kidney biopsies, 1,078 were males (56.0%) and the mean age was 37.7 ± 16.5 years. Asymptomatic urinary abnormalities were the most common clinical manifestation (62.5%). Immunoglobulin A nephropathy (IgAN) was the most common primary glomerular disease (37.4%), followed by minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulonephritis and crescentic glomerulonephritis. Secondary glomerular diseases accounted for 10.3% of the total biopsies, with lupus nephritis being the most common (4.6%) followed by Henoch-Schönlein purpura nephritis and diabetic nephropathy. The most common cause of nephrotic syndrome was MCD (42.1%) followed by MN. Among patients seropositive for hepatitis B or C, IgAN (28.3% and 21.4%, respectively) was the most common cause.ConclusionIgAN and lupus nephritis were the most common primary and secondary glomerular diseases, respectively. Race, region, and practice patterns may affect renal disease patterns in different cohorts.

POS-388 Role Of Serum Galactose Deficient IgA1 As A Noninvasive Biomarker For Diagnosis Of IgA Nephropathy And Its Role In Assessing The Genetic Susceptibility Of Disease

We carried out a retrospective analysis of kidney biopsies done in our institute between January 2016 and June 2021, and clinical and histopathological correlation was done from the available medical records. Of the 411 kidney biopsies evaluated, 56.7% were females and the mean age of patients was 31.65 years. The elderly population (age ≥60 years) constituted 5% of patients. The most common indication for kidney biopsy was nephrotic syndrome (NS) (49.9%). On analysis of histological patterns, 59.3% of patients had primary glomerular disease (PGD), 28% had secondary glomerular disease (SGD), 5.2% had tubulointerstitial disease (TID), and 6.7% had vascular disease. In our study, focal segmental glomerulosclerosis (FSGS) was the most common PGD (28.9% of all PGD) followed by membranous nephropathy (MN) (19.7%), minimal change disease (MCD) (16.5%), and IgA nephropathy (IgAN) (15.4%). The most common SGD was lupus nephritis (LN) (23%) followed by diabetic nephropathy (DN) (1.99%). In patients aged ≤18 years, MCD was the most common PGD (26.5%) and FSGS was the most common PGD (30%) in patients aged between 19 and 59 years. In the elderly population (age ≥60 years), MN was the most common (38%) PGD. This is the largest study of kidney biopsies patterns from the central part of India, and it presents the combined analysis of the clinical, histopathological, and immunofluorescent features of biopsy-proven kidney diseases in our population.

To search for biomarkers of IgA nephropathy, protein profiles of urine samples from patients with IgA nephropathy and normal volunteers were compared using two-dimensional DIGE. Most of the 172 spots identified in the urine were serum proteins, and their amounts in IgA nephropathy urine were much higher than those in normal urine; this can be explained as proteinuria caused by glomerular dysfunction. However, only alpha(1)-microglobulin, also one of the major serum proteins, in IgA nephropathy urine was not higher in amount than that in normal urine. We confirmed using ELISA analysis that the amounts of transferrin and albumin in IgA nephropathy and diabetic nephropathy urine were much higher than those in normal urine, whereas the amount of alpha(1)-microglobulin in IgA nephropathy urine was not higher than that in normal urine and was much lower than that in diabetic nephropathy urine. Approximately 50% of alpha(1)-microglobulin forms a complex with IgA in serum. These results suggest that alpha(1)-microglobulin in IgA nephropathy urine is a characteristic protein and might be a biomarker for IgA nephropathy and that alpha(1)-microglobulin might have a relationship with IgA nephropathy pathology.

IgA nephropathy is the most common primary GN worldwide and is a frequent cause of ESKD, especially in Asia. Work performed over the past few decades has led to significant advances in the understanding of common steps in its pathogenesis. Currently, the best predictors of progression are histologic

Serum immunoglobulin G provides early risk prediction in immunoglobulin A nephropathy

Objective The clinical data of postoperative perirenal hematoma after renal biopsy in recent 10 years were retrospectively analyzed,and its relationship with pathological type was explored.Methods From April 2003 to April 2013,2062 patients of renal biopsy were enrolled and divided into 3 groups:youth group (18-39 years,1634 cases),middle age group (40-59 years,323 cases) and aged group (≥60 years,105 cases).Relationship between renal hematoma and pathology was analyzed.Results There were 1370,255,69 cases of primary glomerular disease respectively in 3 groups,and 264,68,36 cases of secondary glomerular diseases.Three hundred and seventy-nine in all patients were complicated with perirenal hematoma,and the incidence rates were 15.8％ (325/2062),1.8％ (37/2062),0.8％ (17/2062) respectively.Incidence rate of hematoma in primary glomerular disease was higher than that in secondary diseases [19.0％ (322/1694) vs.15.5％ (57/368)].Three most common primary glomerular disease in which perirenal hematoma occured was IgA nephropathy 7.4％ (126/1694),focal/segmental lesions 4.2％(71/1694) and membranous nephropathy 2.4％ (41/1694); while the incidence rate of lupus nephritis hematoma was as high as 9.0％ (33/368).Conclusion Single-center data shows that the most common pathology types of perirenal hematoma are lupus nephritis,IgA nephropathy,focal/segmental lesions and membranous nephropathy. Key words: Biopsy, needle; Hematoma; Kidney; Pathologic types

Glomerular diseases are numerous and difficult to diagnose without a renal biopsy. Despite the development of many radiological and laboratory tests and the use of up-to-date equipment, renal biopsies are the best method for diagnosing renal diseases. This study aimed to analyze the histopathological patterns of glomerular diseases in Oman. Light microscopy and immunofluorescence markers such as immunoglobulin (Ig) G, IgA, IgM, C3, and C1q, which are routinely used to evaluate the presence of immune deposits, were analyzed. In total, 596 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital for a 5-year period (2011-2015). Males represented 45.8%, and the median age was 29.7 years. Primary glomerular diseases were more common in males (54%); secondary glomerular diseases were more prevalent among females (76.7%). The prevalence of primary glomerular diseases (65.6%) was more dominant than secondary glomerular diseases (34.4%). Lupus nephritis (LN) was the most common secondary glomerular disease and was the most prevalent among all biopsies (29.9%). Focal segmental glomerulosclerosis (FSGS), membranous glomerulopathy, IgA nephropathy, minimal change disease, and diffuse global glomerulosclerosis were the most common primary glomerular diseases, accounting for 21.5%, 9.1%, 8.6%, 6.4%, and 6.2%, respectively. The level of the fluorescein isothiocyanate C1q marker in the top five renal diseases was low compared with other markers. In conclusion, in Oman, LN was the most common glomerular disease encountered and FSGS was the most common primary glomerular disease. The findings suggest that the localization of glomerular C1q in renal diseases needs to be investigated further.

IgA nephropathy (IgAN) is one of the most common immune-related primary glomerular diseases. The pathological mechanism of this disease is complex, and the specific pathogenesis is still unclear. To obtain a comprehensive understanding of its molecular mechanism and to provide new perspectives regarding the detection and treatment of the disease, this study investigated the role of immune cells in IgAN, as well as the role of autophagy-related biomarkers in IgAN development. The original datasets GSE93798, GSE35487, GSE58539, GSE116626 and GSE115857 were downloaded from Gene Expression Omnibus (GEO) and were further integrated and analyzed. The differentially expressed genes (DEGs) between IgAN and healthy control (HC) group were identified by the “limma” R package. The gene ontology (GO) function, Kyoto Encyclopedia of Genes and Genome (KEGG) pathway, GeneSet Enrichment Analysis (GSEA) and DisGeNet enrichment were adopted to analyze the genes from the intersection of DEGs. The hub genes were screened by the square least absolute shrinkage and selection operator (LASSO) and cross validation. Immune cell infiltration was analyzed using CIBERSORT. The correlation between hub genes and infiltrating immune cells was calculated by R software. For the purpose of exploring the value of hub genes for diagnosing IgAN, a receiver operating characteristic (ROC) curve was constructed. Finally, Real-time quantitative polymerase chain reaction (qRT-PCR) was used to verify the relative mRNA level of the AT-DEGs. 12 DEGs were screened out. Enrichment analysis revealed that autophagy-related DEGs (AT-DEGs) were mainly related to intrinsic apoptotic signaling pathway, cellular response to external stimulus, transcription repressor complex and other cellular functions, KEGG pathways enriched by AT-DEGs mainly included biological metabolic pathways related to autophagy, while DisGeNET analysis showed that these AT-DEGs were mainly related to immunological diseases. The optimal six hub genes were obtained by lasso analysis as potential biomarkers for IgAN. ROC curve analysis showed that 4 of the 6 HUB genes had great diagnostic value. Immune infiltration results showed B cells memory, macrophages M2, NK cells activated, T cells CD4+ memory resting, and monocytes are the predominant immune cells with the development of IgAN. The qRT-PCR results showed that, compared to the NC group, SIRT1 mRNA expression in PBMCs from IgAN patients was significantly reduced, while BAG3, CDKN1A, and FOS mRNA levels were markedly elevated. SIRT1, BAG3, COKN1A and FOS can be considered as effective biomarkers related to autophagy for the diagnosis of IgAN. These findings suggest some potential new serum biomarkers for IgAN diagnosis.

BackgroundGlomerular diseases show global variation in presentation, pathophysiology, and progression. IgAN (IgA nephropathy), the most common primary glomerular disease with higher prevalence in Asians, remains poorly understood regarding its clinical profile, immunopathogenesis, and treatment.ObjectivesThe aim is to study the spectrum histopathological diagnosis of kidney diseases among patients undergoing native kidney biopsy at Tribhuvan University Teaching Hospital, Institute of Medicine (TUTH, IOM) and compare clinical profile of IgA Nephropathy (IgAN) with other primary glomerular diseases i.e. MCD (Minimal Change Disease), FSGS (Focal Segmental Glomerulopathy, MN (Membranous Nephropathy) and C3 glomerulopathy.Materials and methodsThis quantitative longitudinal study was conducted at TUTH, IOM (May 2022–April 2023) on consecutively sampled patients with glomerular diseases undergoing native kidney biopsy. After informed consent, participants underwent clinical evaluation, lab tests, and imaging. Patients without consent or failed/inconclusive biopsies were excluded. Biopsies were analyzed at Dr. Lal Path Labs, India using standard protocols for light, immunofluorescent, and electron microscopy. Data was analyzed using SPSS v28 (Statistical Package for Social Science).ResultsThis study analyzed 223 native kidney biopsy patients (aged 12–81 years, mean 36.3 ± 15.9) with glomerular diseases, showing female predominance (male: female = 1:1.6) and peak incidence in the 20–40 age group (52%). Nephrotic syndrome was the leading biopsy indication (42.2%), followed by nephritic syndrome (16.1%). IgAN (25.1%) and lupus nephritis (21.1%) were most common, followed by FSGS (10.3%), MN (8.1%), and MCD (7.2%). Comparative analysis revealed IgAN presented later than other primary GNs from symptom onset (9.5 ± 6.42 vs. 4.18 ± 3.53 months, p = 0.001) and had stronger associations with hypertension (p = 0.04), nephritic syndrome (p = 0.049), microscopic hematuria (p = 0.001), and unexplained kidney impairment (p = 0.004). IgAN patients had significantly higher serum creatinine (211.36 ± 187.57 mmol/L vs. 112.41 ± 82.91 mmol/L, p = 0.001), lower hemoglobin (12.19 ± 2.07 g/dL vs. 13.26 ± 2.39 g/dL, p = 0.01), and reduced eGFR (63.8 ± 42.7 mL/min/1.73 m² vs. 83.81 ± 38.25 mL/min/1.73 m², p = 0.009) but preserved serum albumin (34.3 ± 6.85 vs. 29.79 ± 8.16 g/L, p = 0.001) compared to other primary GNs. No significant differences were found in demographic distribution, proteinuria, or serological markers between groups.ConclusionNephrotic syndrome was leading kidney biopsy indication. IgAN was the most common histological finding, followed by lupus nephritis. Primary GN was more prevalent than secondary GN. IgAN had a distinct clinical and laboratory profile. The findings emphasize establishing national kidney biopsy registry in Nepal to standardize data and track longitudinal outcomes.Clinical trial numberNot applicable.

Highlights1.IgA nephropathy is a common glomerular disease and a leading cause of progression to end-stage renal disease.2.BAFF and APRIL induce excessive B-cell activation by binding to receptors TACI, BCMA, and BAFF-R, leading to the overproduction of galactose-deficient IgA1 (Gd-IgA1).3.Mechanism of action of BAFF/APRIL biological agents in treating IgA nephropathy.4.Clinical trial progress of BAFF/APRIL biological agents in treating IgA nephropathy.IgA nephropathy (IgAN) is the most common primary chronic glomerular disease worldwide. Its clinical features include proteinuria and complement pathway activation, which are the strongest predictors of progression to renal failure. This disease can occur at any age. Approximately 30–40% of IgAN patients progress to end-stage renal disease (ESRD) within 20–25 years after diagnosis, making it one of the major causes of ESRD. As understanding of the autoimmune development of IgA nephropathy (IgAN) grows, research shows that BAFF and APRIL promote B-cell activation by binding to the receptors TACI, BCMA, and BAFF-R. This results in the overproduction of galactose-deficient IgA1 (Gd-IgA1), which helps drive the progression of IgA nephropathy. B-cell and plasma cell-targeted therapies, such as biologics against BAFF/APRIL, can precisely and effectively improve patient symptoms. Corresponding agents have now been successfully developed and are administered via subcutaneous or intravenous injection. Clinical trials have demonstrated the significant effectiveness of this approach, especially in reducing proteinuria, stabilizing eGFR, and lowering Gd-IgA1 levels. Although current trial data for BAFF/APRIL-targeted biologics in IgA nephropathy are promising, these new treatments need ongoing clinical monitoring for long-term infection risks and potential drug resistance. This article focuses on the application of BAFF/APRIL biologics in the treatment of IgA nephropathy, addressing gaps in existing literature. While prior studies have emphasized the mechanisms of action of these drugs in IgA nephropathy, they have lacked a comprehensive summary of the current status of specific drug research and clinical progress.

Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and a significant proportion of patients develop kidney failure within 30 years. Circulating undergalactosylated IgA, a key driver of IgAN, has been shown to induce endothelial damage. Glomerular endothelial activation is believed to contribute to complement activation and potentially contribute to disease progression. However, the clinical utility of plasma endothelial biomarkers in IgAN is unclear and no study has analyzed the relationship between endothelial biomarkers and loss of kidney function over time in IgAN. We aimed to study the association between plasma endothelial biomarkers at time of kidney biopsy and CKD progression over time, assessed using eGFR slope. We also wanted to compare biomarker levels between patients with IgAN, healthy controls, and disease controls at baseline. Method We conducted a single-center prospective cohort study including 44 patients with IgAN and 19 disease controls, 11 membranous nephropathy (MN) and 8 hypertensive nephropathy (HN), recruited as part of BIONEF-DS, a biomarker study which has consecutively recruited patients undergoing a kidney biopsy at Danderyd Hospital, Stockholm, Sweden, since 2019. We also included 40 age-matched healthy controls (HC). Plasma levels of VCAM-1, ICAM-1, E-selectin, VE-cadherin, and Syndecan 1 were measured at time of biopsy using Meso Scale® (Meso Scale Diagnostics, Maryland, USA), a highly sensitive multi-array assay based on electrochemiluminescence. First, we compared plasma biomarker levels between the four groups and their relation to albuminuria, eGFR and clinical parameters at baseline using Spearman's Rank Order correlation and Kruskal Wallis ANOVA. Secondly, we used linear regression to analyze the association between biomarker levels and eGFR slope amongst patients with IgAN. Results Baseline characteristics of the patients and controls are shown in Table 1. There was no significant difference in age between IgAN patients and HC, whereas patients with IgAN were significantly younger than disease controls (P < 0.0001). Blood pressure was similar in all groups. Kidney function and albuminuria did not differ between IgAN and disease controls, whereas HC had significantly better-preserved kidney function (P < 0.0001) and no albuminuria. Patients with IgAN had significantly higher levels of ICAM-1, VCAM-1, Syndecan-1 and Thrombomodulin compared to HC (P = 0.02 for ICAM-1; P < 0.001 for others) but similar levels to disease controls. Amongst patients with IgAN, there were weak positive correlations between U-ACR and E-selectin, VCAM-1 and Syndecan-1 (P < 0.05 for all). There were significant negative associations between all biomarkers and eGFR at baseline (P < 0.05 for all). ICAM-1 levels were significantly lower amongst IgAN patients treated with RAASi (P < 0.01). We found no significant association to MEST-C score. Only three patients were on cortisone at baseline. For the longitudinal part of the study, median follow-up was 3.3 years (2.1–4.1) and median eGFR slope was −1.4 mL/min/1.73 m2/year (−4.1–0.9). There was a significant positive association between E-selectin and eGFR slope (P < 0.05) (Fig. 1). Conclusion We found a significant elevation of key endothelial and glycocalyx biomarkers amongst patients with IgAN compared to healthy controls, with the highest levels found amongst patients with high-grade albuminuria and decreased kidney function. Importantly, patients with IgAN had similar levels of plasma endothelial biomarkers as patients with HN and MN, despite the disease controls being significantly older and with more cardiovascular comorbidities. IgAN patients with the highest levels of E-selectin at baseline improved their kidney function over time, likely as an effect of treatment. Future studies should assess the association between baseline endothelial biomarkers and CKD progression in a larger and more ethnically diverse patient population. It would also be of interest to conduct serial biomarker measurements to study the effect of different therapies on endothelial biomarkers in IgAN.

The pattern of glomerular disease varies worldwide. In the absence of kidney disease/kidney biopsy registry in Nepal, the exact etiology of different forms of glomerular disease is primarily unknown in our country. We analyzed 175 cases of renal biopsies performed from September 2014 to August 2016 in Internal Medicine Ward at B.P. Koirala Institute of Health Sciences. The most common indication for renal biopsy was nephrotic syndrome (34.9%), followed by systemic lupus erythematosus (SLE) with suspected renal involvement (22.3%). Majority of patients were in the 30-60 years' bracket (57.2%), with the mean age of the patients being 35.37 years. The average number of glomeruli per core was 13, with inadequate sampling in 5.1%. Immunoglobulin A (IgA) nephropathy (17%) was found to be the most common primary glomerular disease, followed by membranous nephropathy (14.6%) and focal segmental glomerulosclerosis (14.6%). The most common secondary glomerular disease was lupus nephritis (LN). Complications associated with renal biopsy were pain at biopsy site in 18% of cases, hematuria in 6%, and perinephric hematoma in 4% cases. Although the most common primary glomerular disease was IgA nephropathy, significantly higher population of SLE with LN among Nepalese in comparison with other developing countries warrants further evaluation. As an initial attempt toward documentation of glomerular diseases in the national context, this study should serve as a stepping stone toward the eventual establishment of a full-fledged national registry of glomerular diseases in Nepal.

Background and Aims IgA nephropathy is the most common primary glomerular disease and an important cause of end-stage renal disease. Factors such as decreased renal function, persistent proteinuria, hypertension, and older age predict a poor prognosis in IgA nephropathy. Current international prediction tools for IgA nephropathy determine prognosis based on renal function using estimated glomerular filtration rate (eGFR) at the time of kidney biopsy. However, we observed differences in prognosis between patients with and without concurrent acute kidney injury (AKI) at the time of kidney biopsy. Therefore, we aimed to investigate whether renal function at the time of renal biopsy is a suitable indicator for assessing the long-term prognosis of patients with IgA nephropathy with AKI. Method We retrospectively analyzed a total of 185 patients who were diagnosed with IgA nephropathy between 2009 and 2016 at the Gyeongsang National University Hospital. Clinical data, including pathological, demographic, and laboratory findings of patients, were used. We divided the patients into two groups based on the progression rate of kidney function per year, ‘Progression’ or ‘Non-progression group’. AKI was defined according to the KDIGO Clinical Practice Guidelines. Results Among a total of 185 patients, 113 showed a sustained decline in eGFR of more than 1 ml/min/1.73 m2 per year. The mean eGFR level of the non-progression group was significantly lower than that of the progression group (p = 0.027). The percentage of patients with AKI in the non-progression group was 25%, which was higher than that in the progression group (p < 0.001). The two groups had no significant differences in comorbid disease, medications at kidney biopsy, and treatment. In sub-analysis, the mean eGFR at kidney biopsy was significantly lower than that in the non-AKI group (p < 0.001). The mean estimated risk, calculated by the international prediction tool, was significantly lower in the AKI group. On the other hand, the mean rate of actual GFR decline per year was higher in the non-AKI group (p < 0.001). Conclusion We confirmed a discrepancy between the predicted prognosis and the actual decline in GFR, particularly in the AKI group. We found that AKI at the time of renal biopsy was a good long-term prognostic factor. There is a need to conduct further research to confirm whether this is due to early detection of AKI and early active treatment.