Introduction Chronic kidney disease (CKD) is a major global health burden characterized by immune dysregulation. Peripheral blood lymphocyte subsets can reflect immune status across CKD pathologies. We evaluated associations between lymphocyte subsets and clinical parameters in patients undergoing renal biopsy in a contemporary cohort. Methods We conducted a retrospective cross-sectional study of adults (≥16 years) who underwent native renal biopsy at Tongji Hospital, China, from January 2012 to December 2024. The lymphocyte subsets assessed by flow cytometry included combined T/B/NK cells (TBNK), total T cells (CD3⁺CD19⁻), total B cells (CD3⁻CD19⁺), helper T cells (CD3⁺CD4⁺), cytotoxic T cells (CD3⁺CD8⁺), and natural killer cells (CD3⁻CD16⁺CD56⁺). Clinical data included demographics, comorbidities, medications, clinical and immunological markers. Multivariable linear regression was employed to investigate the relationships between lymphocyte subsets as continuous variables and clinical parameters, and nested regression using quartile categories to assess dose-response relationships. Results In total, 1,033 individuals were enrolled. TBNK levels declined with age (β = −4.33, 95% CI: −7.35 to −1.32) and were lower in females than males (β = −84.26, 95% CI: −157.29 to −11.23). Lymphocyte subset distributions varied by nephritis pathology: ANCA-GN and LN showed lower levels than other types, whereas purpura nephritis was relatively higher. TBNK counts correlated positively with eGFR (β = 11.48, 95% CI: 6.78 to 16.19), with similar patterns for total B, total T, CD4+ T, and CD8+ T cells. Lymphocyte counts were also positively associated with complement 3. Among IgAN, TBNK levels correlated positively with IgA (β = 0.31, 95% CI: 0.06 to 0.57) and complement 3 (β = 0.10, 95% CI: 0.06 to 0.14). Conclusions Lymphocyte and subset counts relate to renal function, immune indices, and pathology. Their measurement may help evaluate disease severity and immune status in nephritis and inform clinical management.

ObjectiveTo accurately assess the importance of glomerular filtration rate in the elderly population， explore the clinical characteristics of the elderly population who need to monitor glomerular filtration rate， and verify the performance of the currently commonly used estimated glomerular filtration rate （eGFR） formula.MethodsA total of 313 patients aged 60 years and older who underwent 99mTc-DTPA renal dynamic imaging for measured glomerular filtration rate （mGFR） in Tongji Hospital， Tongji Medical College， Huazhong University of Science and Technology from December 1， 2012 to December 31， 2021 were enrolled. The characteristics of elderly patients were analyzed. The consistency， precision and accuracy of commonly used eGFR formulas and mGFR were analyzed. Bland-Altman plots were used to compare the deviations between eGFR values calculated by each formula and mGFR values. The accuracy of each formula was evaluated by the proportion of eGFR within mGFR （1 ± 10%） （P10）， the proportion within （1 ± 30%） （P30）， mean percent error （MPE）， and mean absolute percent error （MAPE）. The deviations between the formulas were compared using the t-test， and the differences in P10 and P30 between the formulas were compared using the McNemar test.ResultsResults The age of the elderly population in this study was 68.3（63.0，72.0） years. All the commonly used eGFR formulas overestimated mGFR to varying degrees. The interquartile range （IQR）， MPE， MAPE， and root mean square error （RMSE） of the residual （eGFR-mGFR） were used to evaluate the accuracy of the formula eGFR. Both the Cockroft-Gault formula and the EKFC formula showed higher accuracy， among which the Cockroft-Gault formula had the lowest MPE and IQR， and the EKFC formula had the lowest MAPE and RMSE. The percentage of patients with absolute percentage errors within 10% and 30% was used as an indicator to evaluate the accuracy performance of the eGFR formula. Both the EKFC formula and the BIS1 formula showed higher accuracy， among which the EKFC formula had the highest P10 （26.8%）， and the BIS1 formula had the highest P30 （67.4%）. The C-MDRD formula performed the worst in both accuracy and precision.ConclusionAll commonly used eGFR formulas overestimate mGFR in the elderly to varying degrees. In general， the EKFC formula has better performance in accuracy and precision， and the accuracy P30 of the EKFC formula is higher than that of the Cockroft-Gault formula， while the C-MDRD formula performs the worst in both accuracy and precision.

Studies have found that there is tertiary lymphoid structure (TLS) in IgA nephropathy (IgAN), and the existence of TLS has an impact on renal function, creatinine, and proteinuria in patients. We aim to explore the potential molecular mechanisms and therapeutic targets of TLS in IgA nephropathy by bioinformatics methods, hoping to provide treatment methods. The datasets GSE226840, GSE237120, and GSE116626 from the Gene Expression Omnibus (GEO) database were employed to investigate the potential therapeutic targets of TLS in IgAN. The R was used to obtain the differentially expressed genes (DEGs) of three datasets, and the Venny was used to intersect the above three parts of the DEGs to obtain the common DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on obtained genes using Metascape. Protein-Protein interaction (PPI) network was constructed. The intersection of the above common differential genes and IgAN differential genes was obtained by Venny tool. The Nephroseq platform was used to screen core genes and explore their relationship with clinical features. Meanwhile, CIBERSORT was utilized to further delve into the correlation between core genes and immune cells. 92 TLS-related genes and 486 IgAN related genes were obtained, and 6 common genes were obtained after crossing the two genes. The intersection genes were verified by Nephroseq, and CDKN1A, CD83, DUSP6, and CD48 were identified as core genes. At the same time, there were differences in the composition of immune cells between the disease group and the control group when the immune infiltration analysis was performed. And by further analyzing the correlation between core genes and immune cells, the study found that the four genes were positively correlated with T cells, B cells, plasma cells, and other immune cells. By exploring the relationship between core genes and clinical features, CDKN1A and DUSP6 were negatively correlated with Glomerular Filtration Rate (GFR) and positively correlated with proteinuria in IgAN patients. CD48 was negatively correlated with GFR and positively correlated with Blood Urea Nitrogen (BUN). The four genes highly associated with TLS and IgAN were screened using GEO database in study. And CDKN1A, CD83, DUSP6 and CD48 may provide potential therapeutic targets for the treatment of TLS in IgAN. At the same time, studies have found that T cells, B cells, and macrophages may be involved in the formation of TLS in IgAN.

Background: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN. Methods: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a >= 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis. Results: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016). Conclusion: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

ABSTRACT Background Microangiopathy (MA) lesions are not rare in immunoglobulin A nephropathy (IgAN) and have been suggested to have a potential role in increasing risk in renal function decline. However, this suggestion has not been universally accepted. We aimed to investigate its role in our cohort and in multiple studies through a systematic meta-analysis. Methods This cohort study included 450 IgAN patients, confirmed by renal biopsy, at Tongji Hospital, China, from January 2012 to December 2016. Clinical data were collected and analysed. We systematically searched PubMed and Web of Science for studies investigating the association between MA lesions and IgAN. Results In our cohort, IgAN patients with MA were significantly older and had higher blood pressure, more proteinuria, worse kidney function and increased uric acid levels compared with patients without MA. When comparing pathological features with the non-MA group, the MA group exhibited more global glomerulosclerosis and interstitial fibrosis/tubular atrophy. MA lesions were independently associated with a composite kidney outcome in IgAN patients {adjusted hazard ratio 2.115 [95% confidence interval (CI) 1.035–4.320], P = .040}. Furthermore, this relationship was validated in a meta-analysis involving 2098 individuals from five independent cohorts. The combined data showed a 187% adjusted risk of poor renal outcome in IgAN patients with MA compared with patients without MA [adjusted risk ratio 2.87 (95% CI 2.05–4.02; I2 = 53%). Conclusion MA lesions could serve as a valuable predictor for disease progression in patients with IgAN, extending beyond the widely recognized Oxford MEST-C score.

Background and Aims: Steatosis is a common histopathological feature of chronic hepatitis B (CHB), and has been associated with the severity of liver disease.Recently, the rs738409 I148M PNPLA3 polymorphism has been demonstrated to influence steatosis susceptibility and fibrosis progression in patients with obesity, alcohol abuse, and chronic hepatitis C, but no data are yet available for CHB.Aim: To evaluate whether PNPLA3 I148M influences steatosis susceptibility in a large series of patients with biopsy proven CHB.Methods: 235 treatment-naïve CHB patients consecutively examined by percutaneous liver biopsy were enrolled.In ≥2 cm long liver tissue cores, steatosis and fibrosis were staged by Kleiner and METAVIR scores, respectively.The I148M polymorphism was determined by Taqman assays.Results: Steatosis was present in 146 (62%) patients, of whom 22 (10%) had severe steatosis, i.e. involving >33% of hepatocytes.Steatosis was independently associated with age (OR 2.67, 1.50-4.92for age≥50 years), BMI (kg/m 2 ; OR 2.84, 1.30-6.76for BMI ≥27.5), diabetes or impaired fasting glucose (OR 4.45, 1.10-30.0),and PNPLA3 148M allele (OR 1.62, 1.00-7.0for each 148M allele).Independent predictors of severe steatosis were BMI (OR 3.60, 1.39-9.22for BMI ≥27.5 kg/m 2 ), and PNPLA3 148M allele (OR 6.03, 1.23-5.0for each 148M allele).PNPLA3 148M alleles were associated with a progressive increase in severe steatosis in patients with, but not in those without, acquired cofactors such severe overweight and a positive history of alcohol intake (p = 0.005).Conclusions: In CHB patients, the PNPLA3 I148M polymorphism influences the susceptibility to steatosis, and, in particular when associated with severe overweight and positive alcohol intake, to severe steatosis.