The clinical courses of BK polyomavirus nephropathy (BKPyVN) are variable. This study aimed to evaluate the usefulness of repeat donor-derived cell-free DNA (dd-cfDNA) monitoring in identifying clinical courses. Repeat allograft biopsy and dd-cfDNA monitoring were performed at 6-12 months post-intervention or when renal allograft dysfunction occurred. Results demonstrated that recipients with rejection had a higher plasma dd-cfDNA fraction (2.23% [1.17%, 5.52%]; n = 13) than those with resolved BKPyVN (0.80% [0.66%, 0.91%]; n = 30; p < 0.001) or persistent BKPyVN (0.82% [0.61%, 1.12%]; n = 10; p = 0.002). Compared to baseline at BKPyVN diagnosis, urine dd-cfDNA concentration decreased in recipients with resolved BKPyVN post-intervention (3.90 [1.35, 5.80] ng/mL vs. 7.88 [6.00, 15.37] ng/mL; p < 0.001), but not in persistent BKPyVN (9.02 [5.26, 10.35] ng/mL vs. 7.96 [6.43, 10.21] ng/mL; p = 0.463). Changes in urine dd-cfDNA concentration were positively correlated with changes in the extent of SV40 LTag-positive staining, while changes in plasma dd-cfDNA fraction positively correlated with changes in glomerulitis score. A plasma dd-cfDNA fraction > 1.12% following BKPyVN intervention could identify rejection (AUC = 0.924), and a urine dd-cfDNA concentration > 5.95 ng/mL could identify persistent BKPyVN (AUC = 0.840). In summary, repeat dd-cfDNA monitoring integrated with clinical data can serve as an adjunct to identify BKPyVN clinical courses.

Introduction:Solitary fibrous tumors (SFTs) generated from uterine corpus are extremely rare and hard to distinguish from myomas, but their prognoses are wildly different. Doege-Potter syndrome (DPS) is a form of nonislet cell tumor hypoglycemia (NITCH) caused by a SFT. Vigilance is required when a pelvic mass is found concurrent with NITCH. Case Presentation:A 65-year-old female with huge pelvic masses generated from uterine corpus presented with mild symptoms of transient slow response, accompanied by memory loss once, and was found to have hypoglycemia. The pituitary glucocorticoid axis, pituitary sex hormone axis, and pituitary growth hormone axis functioned normally; insulin release was normal, but relatively low insulin levels indicated suppression of secretion. Abdominal total hysterectomy and bilateral salpingo-oophorectomy were performed, and pathology confirmed a benign SFT with DPS. Blood glucose levels after surgery are significantly elevated and more stable. This case fell into the intermediate-risk group, but the disease recurred. Cytoreduction surgery was performed 13 months after initial treatment without DPS. Discussion:Uterine corpus-generated SFTs are hard to distinguish preoperatively. However, complete tumor resection is a key prognostic factor because SFTs have a risk of long-term recurrence. DPS can be a differential diagnostic point, but there is no significant relation between tumor burden and recurrence.

Background:Kidney allograft rejection exhibits highly complex features due to the intricate immune mechanisms involved. The early and accurate diagnosis of rejection remains challenging, particularly when differentiating between/among subtypes. Herein, the authors present "RenalTransPredNet," an interpretable model that integrates whole-slide images with routine clinicopathological variables to diagnose kidney allograft rejection. Methods:This study included kidney allograft biopsies performed at the Headquarters and Lingnan Hospital of the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and August 2024. After screening, 1086 digital whole-slide images from 362 biopsies and their corresponding clinicopathological information were analyzed, comprising 209 other lesions and 153 rejections. By integrating multiple instance learning-based pathological image analysis with random forest-based clinicopathological information analysis, RenalTransPredNet was used to efficiently construct models for kidney allograft rejection-related multiclass and binary classification tasks. Results:RenalTransPredNet achieved a higher area under the curve (AUC) value than both the pathological imaging and clinicopathological information models in detecting and subtyping kidney allograft rejection, yielding an AUC of 0.886 using data from the internal testing set. For the prediction of treatment response to rejection, RenalTransPredNet yielded an AUC of 0.743. In the task predicting graft loss after rejection, RenalTransPredNet demonstrated predictive capabilities for graft loss at 1, 2, 3, and 5 years post-rejection, with AUCs of 0.876, 0.942, 0.904, and 0.978, respectively. Conclusion:These findings support the potential of RenalTransPredNet in improving the diagnostic accuracy of pathologists in detecting and subtyping kidney allograft rejection and in contributing to prognostic assessments.

Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a novel renal tumor entity incorporated in the 2022 WHO classification with a female predilection. To further investigate its morphological and molecular features, we analyzed 17 ESC RCC cases with comprehensive morphological, clinicopathological and next-generation sequencing data, and reviewed 63 previously reported cases with confirmed TSC gene mutations. Clinically, our cohort had a male-to-female ratio of 1.4:1. Fifteen patients with a median follow-up of 55 months (range, 5-144 months) remained disease-free. Morphologically, 10/17 tumors showed classic solid-cystic growth and 7/17 showed predominant solid growth. Two distinctive morphological features were identified: a novel phenotype of condensed eosinophilic cytoplasm forming inclusion-like appearance (5 cases) and the recently described xanthomatous giant cell feature (4 cases). Immunohistochemically, CK20 was positive in 15/17 cases, and all cases showed strong positivity for mTOR downstream markers (GPNMB, p-S6, p-4EBP1). Molecularly, TSC1 mutations were detected in 8/17 cases, and TSC2 mutations in 9/17. All 5 cases with condensed eosinophilic cytoplasm uniformly harbored TSC1 mutations. Analysis of our 17 cases and 63 reported cases showed TSC2 mutations in 50/80 (62.5%), TSC1 mutations in 31/80 (38.8%), and concurrent TSC1/2 mutations in 1/80 (1.3%). Totally 110 distinct mutation sites were found with only 7.3% being repeatedly reported in no more than 3 patients. Truncating variants (frameshift, nonsense, splice site) were the predominant type (90.9%), while missense mutations only account for 9.1%. Collectively, our research expanded the morphological spectrum of ESC RCC, depicted a wide molecular mutation landscape and confirmed its indolent behavior without gender predilection in Chinese patients.

Primary renal synovial sarcoma (PRSS) is an extremely rare neoplasm that presents considerable diagnostic challenges due to its morphological overlap with other renal tumors. In this multicenter study, 23 PRSS cases with confirmed SS18::SSX rearrangements and 112 non-PRSS renal tumors were included. Clinicopathological features and immunohistochemical expression were evaluated. Diagnostic performance of individual markers and their combinations was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, and a practical diagnostic approach for PRSS was proposed. The cohort (n = 23) had a median age of 42.3 years with slight male predominance (56.5

Introduction: Interstitial fibrosis and tubular atrophy (IFTA) are common pathological findings in patients with malignant hypertension (mHTN)-related thrombotic microangiopathy (TMA), but their predictive value for renal outcomes in this population remains unclear. Methods: This study included patients with mHTN-related TMA confirmed by renal biopsy, admitted to seven different Chinese hospitals from January 2008 to October 2024. Patients were stratified into mild/moderate, severe, and extremely severe IFTA groups based on renal biopsy findings. The primary outcome was renal replacement therapy (RRT) dependence during follow-up, while the secondary outcome was renal function recovery. Results: A total of 465 patients (median age: 35 years, 87.74% male) were included in this study. During a median follow-up of 24 months, RRT dependence occurred in 182 patients and renal function recovery occurred in 226 patients. Kaplan-Meier analysis showed higher RRT risk with more severe IFTA. Cox regression models showed that severe and extremely severe IFTA groups had hazard ratios of 2.29 (95% CI: 1.59-3.28) and 8.00 (95% CI: 5.36-11.95) for RRT dependence compared to mild/moderate IFTA group (both p < 0.05), even after adjusting for clinical variables and the proportion of global glomerulosclerosis. The cumulative probability of renal function recovery also differed among IFTA groups (log-rank p < 0.001). Extremely severe IFTA negatively impacted renal function recovery in unadjusted analysis, but this significance disappeared after adjusting for the proportion of global glomerulosclerosis. Conclusion: IFTA may serve as a valuable and independent predictor of renal outcomes in patients with mHTN-related TMA, highlighting its importance for clinical decision-making.

This observational cohort study aimed to identify factors influencing long-term renal outcomes in 170 patients with biopsy-proven malignant hypertension (MHT)-associated renal thrombotic microangiopathy (TMA) who were dialysis-independent at baseline, recruited between 2008 and 2023. Over a median follow-up of 23.5 months, 52 patients (30.6%) progressed to end-stage renal disease (ESRD). Those developing ESRD exhibited significantly higher total cholesterol levels, heavier proteinuria, a greater proportion of global glomerulosclerosis, more advanced interstitial fibrosis/tubular atrophy, and lower baseline eGFR, along with lower use of renin-angiotensin-aldosterone system (RAAS) inhibitors. In Cox regression analysis, elevated total cholesterol (HR = 1.48 per 1 mmol/L change; 95% CI: 1.24-1.77, p < 0.001) and a higher percentage of glomerulosclerosis (HR = 1.24, 95% CI: 1.15-1.33, p < 0.001; per 5% increase of glomerulosclerosis) were independent risk factors for ESRD, while RAAS inhibitor use was associated with a significantly reduced risk (HR = 0.45, 95% CI: 0.25-0.82, p = 0.009). These findings underscore the prognostic value of lipid profiles and histologic injury severity in MHT-associated TMA and support the protective role of RAAS blockade in preserving renal function, which may guide risk stratification and therapeutic decisions in this high-risk population.

BACKGROUND:Focal segmental glomerulosclerosis (FSGS), which can be caused by many etiologies, is one of the major causes of nephrotic syndrome and end-stage kidney disease. Multiple etiologies, including glomerular hyperperfusion, can cause secondary FSGS. Unilateral renal artery stenosis can lead to FSGS of the contralateral native kidney, but it is not well demonstrated whether transplant renal artery stenosis can cause a similar change in a single transplanted kidney. CASE PRESENTATION:A female underwent kidney transplantation at the age of 17 on January 14, 2020. Her renal function remained stable until 25 months later, when the patient presented with hypertension and elevated serum creatinine (SCr), with an unremarkable urine test. Ultrasound and computed tomography angiography (CTA) revealed stenosis at the initial segment of the main transplant renal artery. After percutaneous transluminal angioplasty of the main transplant renal artery, her SCr and blood pressure recovered. 5 months later, hypertension recurred with moderate proteinuria (2.5 g/d). An allograft biopsy showed a remarkable cellular FSGS lesion. Due to the absence of glomeruli in the electronic microscope sample, a second biopsy was performed a month later. Unexpectedly, no FSGS, except for very mild glomerular hypoperfusion and remarkably enlarged juxtaglomerular apparatus, was found. Hemodynamic abnormality in the kidney was suspected as the two biopsy sites were from the lower pole and upper pole, respectively. The donor kidney had an accessory renal artery on a common aortic patch with the main renal artery. Doppler ultrasonography confirmed two different hemodynamic areas in the kidney. Transplant renal artery stenosis of the main artery induced an FSGS lesion in the region dominated by the accessory artery. Endovascular stenting was performed, and her proteinuria turned negative, with SCr recovering only 3 days later. The patient had long-term follow-up after discharge and had a favorable condition. CONCLUSIONS:Transplant renal artery stenosis can cause regional hyperperfusion leading to adaptive FSGS, presenting with proteinuria and morphologically manifesting as a cellular variant of FSGS instead of the classic variant, which is usually closely related to hyperperfusion. The lesion must be differentiated from primary and other secondary FSGS. Removal of the hemodynamic abnormality can quickly relieve hypertension and proteinuria.

While a few studies have investigated renal manifestations associated with mitochondrial DNA (mtDNA) mutations, detailed renal histopathological changes and long-term outcomes remain poorly characterized. This study reported a family in which all the five siblings presented with hyperuricemia and chronic kidney disease (CKD); the proband died of kidney failure at 16 years of age, while both parents were unaffected. Renal histology from three siblings revealed multiple foci of sclerotic and atubular glomeruli, as well as focal tubular atrophy, making early pathological diagnosis challenging. Ten years later, whole-exome sequencing identified an m.616T>C mutation in the MT-TF gene of mtDNA, confirming the diagnosis of mitochondrial tubulointerstitial kidney disease and demonstrating mitochondrial abnormalities in the distal tubules and collecting duct. Over a 12-year follow-up period, one patient died of kidney failure, one required dialysis, two progressed from CKD stage G2 to G4, and one remained stable at CKD stage G3. This 12-year study of a family with MT-TF m.616T>C-associated mitochondrial tubulointerstitial kidney disease highlights the relative homogeneity of renal pathology alongside marked heterogeneity in long-term outcomes, despite an identical genetic background.

Background Calcineurin inhibitors (CNIs), such as cyclosporine (CsA) and tacrolimus (TAC), are commonly used to treat children with complicated minimal change nephrotic syndrome. However, chronic nephrotoxicity associated with CNIs poses a significant safety concern. This study aimed to identify the risk factors that contribute to chronic nephrotoxicity in these patients.Material and methods Clinical and pathological data of MCD children treated with CsA or TAC in our center between 1 January 2003 and 31 December 2022, were retrospectively reviewed. Kidney biopsies were performed on 80 patients who received CNI treatment for more than 6 months.Results Chronic CNI nephrotoxicity (striped interstitial fibrosis with tubular atrophy) was observed in 15% (12/80) of patients. Higher CNI culminating amounts were shown in patients who developed nephrotoxicity regardless of CsA or TAC treatment. Risk factors for chronic CNI nephrotoxicity included persistent nephrotic-range proteinuria for more than 30 days during CNI treatment, increased urinary NAG level, and CNI resistance. Multivariate analysis revealed that increased urinary NAG level and CNI resistance were the independent risk factors for chronic CNI nephrotoxicity in children with MCD.Conclusion MCD children who developed CNI resistance were susceptible to chronic CNI nephrotoxicity. Urinary NAG might be a valuable biomarker for CNI nephrotoxicity prediction in MCD children.

Chemoresistance is the main cause of recurrence and metastasis in osteosarcoma patients; therefore, efficient therapeutic measures need to be developed to reverse chemoresistance. In this study, we designed and synthesized selenium-hybrid degradable hollow mesoporous silica nanoparticles (SeNPs) to simultaneously encapsulate doxorubicin (DOX) and carbon monoxide (CO)-releasing molecule-3 (CORM-3), and modified their surfaces with polyethylene glycol (PEG) via disulfide bonds (SeNP-PEG@DOX-CO). Subsequently, after incubation with SeNP-PEG@DOX-CO, DOX was effectively delivered into 143B cells, and CO was released in the mitochondria under the stimulation of high concentrations of glutathione (GSH) and reactive oxygen species (ROS). All in vitro anticancer functional experiments and animal experiments confirmed that DOX had CO-enhanced antitumor efficacy and that CO cooperated with chemotherapeutic drugs to resist tumors. Meanwhile, we provided for the first time a combined proteomic and metabolomic landscape of CO reversing chemotherapy resistance in osteosarcoma. This study revealed a revolutionizing osteosarcoma therapy to treat resistance for chemotherapy.

BACKGROUND:Malignant hypertension (mHTN) is an acute form of hypertension with multiorgan damage, including renal impairment. Renal cortical thickness (RCT) by ultrasonography is associated with renal function in kidney disease. However, the relationship between RCT and renal dysfunction in mHTN is not yet fully understood. DESIGN:A cohort study. SETTING:This was a study conducted between January 2008 and June 2023 at the First Affiliated Hospital of Sun Yat-sen University. PARTICIPANTS:A total of 292 mHTN patients with thrombotic microangiopathy (TMA) who underwent renal biopsy were included in the study. PRIMARY OUTCOMES AND MEASURES:Patient characteristics for RCT were examined using linear regression. The association between RCT and an increase in estimated glomerular filtration rate (eGFR) of ≥15% was analysed by Cox regression. RCT was analysed in two groups classified by median RCT. RESULTS:Overall, patients with larger RCT exhibited a lower global sclerosis ratio and a lower proportion of intravascular thrombosis. RCT was strongly positively correlated with mean kidney length (coefficient B 1.018; 95% CI 0.638 to 1.397; p<0.001), body mass index (BMI) (coefficient B 0.146; 95% CI 0.075 to 0.217; p<0.001) and negatively related to intravascular thrombosis (coefficient B -1.314; 95% CI -2.060 to -0.567; p=0.001) and tubular atrophy/interstitial fibrosis ratio (coefficient B -0.880; 95% CI -1.569 to -0.192; p=0.012). Moreover, larger RCTs had a better renal function improvement of ≥15% increase in eGFR in patients with mHTN with TMA (HR 1.745; 95% CI 1.012 to 3.009; p=0.045). CONCLUSIONS:Smaller RCTs were correlated with a decline in renal function and deterioration of renal pathology. Furthermore, larger RCTs showed a better renal function improvement of ≥15% increase in eGFR in mHTN patients with TMA. RCT may be a predictive factor for renal damage in mHTN.

Chronic kidney disease (CKD) is a global health challenge, but invasive renal biopsies, the gold standard for diagnosis and prognosis, are often clinically constrained. To address this, we developed the kidney intelligent diagnosis system (KIDS), a noninvasive model for renal biopsy prediction using 13,144 retinal images from 6773 participants. The KIDS achieves an area under the receiver operating characteristic curve (AUC) of 0.839-0.993 for CKD screening and accurately identifies the five most common pathological types (AUC: 0.790-0.932) in a multicenter and multi-ethnic validation, outperforming nephrologists by 26.98% in accuracy. Additionally, the KIDS further predicts disease progression based on pathological classification. Given its flexible strategy, the KIDS can be adapted to local conditions to provide a tailored tool for patients. This noninvasive model has the potential to improve CKD clinical management, particularly for those who are ineligible for biopsies.

Up to 10% of renal allograft failures are caused by BK polyomavirus nephropathy (BKPyVN). However, there is no specific antiviral agent for BKPyVN. The only treatment is to reduce the levels of immunosuppression, which is not always practical and increases the risk of rejection. Since targeting the microenvironment is a promising approach, we performed single-cell RNA sequencing (scRNA-seq) on BKPyVN samples and stable allografts to obtain BKPyVN microenvironmental atlases. Interestingly, we identified a novel subpopulation of proximal tubule cells (annotated as IGKC+ PT) with epithelial-immune dual features that may contribute to the progression of BKPyVN through T-cell exhaustion. Additionally, we determined that the IGKC+ PT subpopulation might serve as a non-invasive diagnostic marker through scRNA-seq of urine samples and co-immunofluorescence staining. These results improve our understanding of the BKPyVN microenvironment and may guide the development of new therapeutic and diagnostic approaches for a wide range of patients.IMPORTANCEBKPyVN severely threatens kidney transplant recipients. Due to the lack of effective drugs against BK polyomavirus (BKPyV), reducing immunosuppressant therapy is the only treatment. Unfortunately, this approach is not always effective and increases the acute rejection risk. A growing body of research suggests that potential therapeutic targets may be identified by studying the disease microenvironment. However, traditional methods have not explained why the large number of infiltrating T cells in the BKPyVN microenvironment does not effectively clear BKPyV. Newly available large-scale scRNA-seq technology can be used to study gene expression at a single-cell resolution, offering a new way to investigate the BKPyVN microenvironment. By combining scRNA-seq with experimental analysis, we found a novel subpopulation of proximal tubule cells (annotated as IGKC+ PT) with epithelial-immune dual features that may contribute to the progression of BKPyVN through T-cell exhaustion.

BACKGROUND:Acute rejection (AR) remains a major determinant of renal allograft outcomes, with the major histocompatibility complex (MHC) playing a pivotal role in its pathogenesis. Although immunosuppressive therapies have advanced, their reliance on high doses and lifelong administration increases the risks of infections, malignancies, and other serious complications. Normothermic machine perfusion (NMP) has emerged as a valuable tool in clinical transplantation, enabling organ preservation, functional assessment, and therapeutic intervention. Integrating NMP with genetic engineering approaches to modulate donor kidney MHC expression may offer a novel strategy for preventing AR. METHODS:We synthesized cholesterol-modified small interfering RNA targeting B2m and Ciita (si B2m -Chol and siCiita -Chol) and set cholesterol-modified negative control small interfering RNA (siNC-Chol) as control. Interfering with MHC expression in transplanted kidneys using NMP combined with siB2m-Chol and siCiita-Chol pretreatment of donor kidneys to prevent AR of posttransplant allografts, we evaluated the efficacy of this approach by assessing postoperative survival, renal function, histological features, and inflammatory responses. RESULTS:NMP combined with siB2m-Chol and siCiita-Chol significantly reduced MHC expression on postoperative day 3, improved allograft function, and prolonged recipient survival. By postoperative day 7, pathological damage was reduced, and T cells, macrophages, B cells, donor-specific antibodies, and inflammatory cytokine production were markedly lower in treated grafts compared with the siNC-Chol control group. CONCLUSIONS:These findings demonstrate that ex vivo NMP effectively delivers cholesterol-modified small interfering RNA to renal grafts, substantially downregulating both MHC class I and II expression and consequently attenuating AR.

Introduction Tubular basement membrane (TBM) C4d staining has been frequently observed in BK polyomavirus nephropathy (BKPyVN); however, its specificity and clinical implications remain unclear. Methods Biopsy data from 272 patients with BK viruria, including 4 native BKPyVN, 150 allograft BKPyVN, and 118 non-BKPyVN were reviewed. C4d was assessed using immunohistochemistry (IHC) and compared with frozen tissue to evaluate its correlation with clinicopathological features. Immunofluorescence (IF) for Ig and complement components and electron microscopy were performed to assess complement activation. Results TBM C4d staining was conducted in formalin-fixed paraffin-embedded (FFPE) slides for its superiority over frozen tissue and C4d positivity was detected in all 4 native and 121 kidney transplant recipients (KTRs) (81%) with BKPyVN, significantly higher than the 16 KTRs (14%) without BKPyVN (P < 0.001). Diffuse TBM and Bowman’s capsule C4d staining were restricted to BKPyVN. C4d staining was grouped as no/minimal in 64 of 150 (43%), focal in 51/150 (34%), and diffuse in 35 of 150 (23%) of KTRs. Patients with diffuse TBM C4d staining exhibited higher tissue viral load, more severe chronic tubulointerstitial damage and lower graft survival (all P < 0.05). Multivariable Cox analysis verified that diffuse TBM C4d staining remained independently associated with poor graft prognosis after adjustment. IF confirmed TBM staining of IgG, IgA, C1q, C3c, and C5b-9 in BKPyVN, with colocalization most pronounced in cases with diffuse TBM C4d staining accompanied by electron-dense deposits on EM, whereas nonspecific C5b-9 and C4d staining tended to be entrapped in atrophic tubules. Conclusion TBM C4d positivity is a valuable marker of complement activation in BKPyVN, strongly correlating with the severity of kidney damage and serving as an independent risk factor for graft loss.

Although normothermic machine perfusion (NMP) has been employed in clinical transplantation, the efficient and standardized long-term NMP strategies for small animals remain to be explored, which may significantly facilitate fundamental biomedical research and drug evaluation. We established a straightforward rat kidney ex vivo NMP system and explored the efficacy of different perfusates by comparing various parameters, including the perfusion and metabolic parameters, renal function, histological features, acute renal injury score, and inflammation. Additionally, we implanted the kidneys after NMP and demonstrated the effectiveness and safety by comparing the survival of recipients, acute renal injury, and graft function. The kidneys were able to produce urine during NMP, and the groups with fetal bovine serum (FBS) exhibited higher urine output compared to those supplemented with bovine serum albumin (BSA). Nonetheless, the BSA group displayed more stable perfusion resistance, enhanced oxygen consumption efficacy, superior renal tubule function in electrolyte reabsorption and excretion, and reduced vessel injury and tissue inflammation. All grafts were successfully transplanted, and the BSA group showed slighter injury than FBS on postoperative 1 and 7 days and was not significantly different from the cold storage group. A supporting kidney function in vitro was achieved using the optimized NMP method with the perfusate consisting of rat peripheral blood, RPMI-1640, and BSA. This novel NMP strategy in small animal models may benefit basic studies related to organ preservation, assessment, and intervention in the future.

Immunoglobulin A nephropathy recurrence (IgANR) is a major cause of graft function loss in renal transplant patients with IgA nephropathy. Tonsillectomy has been recognized as an effective treatment for IgANR, but the cellular and molecular effects underlying its efficacy remain poorly understood. We aimed to identify the cell types and gene expression profiles in tonsillar tissue and peripheral blood mononuclear cells (PBMCs) to investigate the effectiveness of tonsillectomy in IgANR treatment. Flow cytometry and single-cell mRNA sequencing were performed to comprehensively characterize the cell types of 29 patients with IgANR. Additionally, we analyzed a tonsillar tissue sample and three PBMC samples to gain further insights. Single-cell transcriptome analysis revealed significant changes in gene expression following tonsillectomy in patients with IgANR. Conventional cytometry and transcriptome analysis revealed that B cells played a crucial role in IgANR treatment using tonsillectomy. Notably, the downregulation of IGHA1 expression, memory B cell inactivation, and alterations in related pathways led to a reduction in galactose-deficient IgA1 (Gd-IgA1), which plays a crucial role in IgA nephropathy. The phosphatidylinositol-3-kinase (PI3k)-Akt pathway was significantly downregulated in peripheral B cells, and peripheral B cells in patients with IgANR who underwent tonsillectomy demonstrated downregulated expression of T cell leukemia/lymphoma 1 A (TCL1A), an Akt coactivator. As a result, it is possible that TCL1A plays a major role in the mediation of this therapeutic effect. Tonsillectomy aids in the treatment of IgANR by guiding B cell phenotypes, inducing functional changes, and regulating the immune response, thereby reducing Gd-IgA1 levels and improving clinical outcomes.