Background: Diabetic kidney disease (DKD) is a significant microvascular complication of diabetes, accounting for the majority of cases of end-stage renal disease. Copper, an essential trace element, has been identified as a factor closely associated with the onset and progression of DKD. However, the precise causal link between serum copper levels and DKD, along with the mechanisms governing their association, remains unclear. Methods: This study employed Mendelian randomization (MR) analysis based on large-scale GWAS data to explore the causal relationship between serum copper levels and DKD. Additionally, mediation analysis was conducted using plasma proteomic data, complemented by enrichment analysis to explore the mediating metabolic pathways or signaling pathways through which serum copper may mediate the development of DKD. Results: MR results demonstrated that elevated serum copper levels significantly increased the risk of DKD (OR = 1.123, p < 0.001). Additionally, no evidence of pleiotropy or heterogeneity was detected, which provides further assurance of the reliability of results. Protein mediation analysis identified 10 plasma proteins, including FABP, Netrin-1, and glutathione S-transferase A4 as critical mediators in copper-driven DKD, with mediation effects ranging from 6.42% to 28.02%. Following the identification of these 10 mediator proteins, 11 intermediary pathways that mediated the effect of serum copper levels on the onset of DKD were identified. Conclusion: This study elucidates the causal effect of copper levels on DKD and reveals the underlying mechanism by which increased serum copper levels lead to the development of DKD, offering novel insights and potential therapeutic targets for DKD prevention and treatment.

IntroductionProliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare subtype of monoclonal gammopathy of renal significance (MGRS). While the IgG subtype has been well characterized, the IgM-κ variant is extremely rare, with a low detection rate of circulating monoclonal proteins and limited real-world data on its clinical course under conservative management. This case report describes a biopsy-proven IgM-κ PGNMID in an elderly patient with negative hematological screening, to expand the current understanding of this rare entity.Patient concerns and diagnosesA 70-year-old male presented with incidentally detected microscopic hematuria and elevated serum creatinine, without overt edema, gross hematuria or systemic symptoms. Renal biopsy demonstrated a membranoproliferative pattern of glomerular injury, with monoclonal IgM deposition showing kappa light chain restriction and negative C3 staining, confirming the diagnosis of PGNMID. Bone marrow biopsy revealed no clonal lymphoplasmacytic proliferation, consistent with MGRS. The patient’s serum creatinine level remained stable with a slight decrease from the baseline value, and the urinary red blood cell count returned to normal.OutcomesAfter 7 months of follow-up, the patient’s serum creatinine levels remained stable with a mild decrease from baseline. This case indicates that IgM-κ PGNMID can present with insidious manifestations and negative conventional hematological screening. For elderly patients with unexplained hematuria and mild renal impairment, early renal biopsy is essential for early identification of rare MGRS lesions, and conservative management may be considered as an initial approach in PGNMID patients with stable mild disease.

Background The proteomic landscape offers insights into potential therapeutic targets for benign prostatic hyperplasia (BPH). We used a Mendelian randomization (MR) approach and colocalization analysis to identify proteins and druggable targets associated with BPH risk.Methods Data from 4,907 circulating proteins in 35,559 individuals were analyzed. Single nucleotide polymorphisms associated with protein levels served as instrumental variables in a summary data-based MR analysis. Colocalization analysis was performed to identify overlapping genetic loci, and the DGIdb database was explored for therapeutic targets.Results MR analysis identified four proteins significantly associated with BPH. Specifically, BTN3A3, BTN3A1, and ASIP were found to be positively correlated with BPH, while RTP4 demonstrated a negative correlation. Colocalization analysis revealed strong support for BTN3A1 and RTP4 with BPH risk loci. The DGIdb database highlighted BTN3A3, BTN3A1, and RTP4 as potential therapeutic targets.Conclusion This study confirms the causal relationship between circulating proteins and BPH, with BTN3A1 as a promising therapeutic target.

Lactate, traditionally regarded as a metabolic byproduct, has emerged as a potential signaling molecule involved in tumorigenesis. Although numerous observational studies have linked serum lactate levels to various tumors, establishing a direct causal relationship remains challenging. We conducted a 2-sample Mendelian randomization (MR) analysis using genetic instrumental variables to assess the causal effects of serum lactate levels on the risk of various cancer types. The primary analytical method used in this investigation was the random inverse-variance weighted (IVW) method, supported by auxiliary methods such as MR-Egger, weighted median, simple mode, and weighted mode, with the IVW method enabling the meta-analysis of their combined effects. To obtain exposure data, we extracted genome-wide association studies (GWAS) data on metabolite levels from the Canadian Longitudinal Study on Aging and the UK Biobank cohorts. Concurrently, GWAS data for 17 types of cancer were obtained from the IEU Open GWAS project and the GWAS Catalog project. Sensitivity analyses were performed using the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and the leave-one-out method. Our MR analysis identified a causal relationship between serum lactate and endometrial cancer (odds ratio [OR]IVW = 1.1217, 95% confidence interval [CI] = 1.0264-1.2258, P = .0112), melanoma (ORIVW = 1.0015, 95% CI = 1.0006-1.0024, P = .0010), and prostate cancer (ORIVW = 0.9578, 95% CI = 0.9319-0.9844, P = .0020). Notably, elevated lactate levels were identified as a risk factor for endometrial cancer and melanoma, while having a protective effect against prostate cancer. However, this observed relationship was not replicated in other cancer types. Our study, using GWAS data, establishes a causal link between circulating lactate and the risk of endometrial cancer, melanoma, and prostate cancer. The identification of these associations suggests the potential utility of lactate as a biomarker for these cancers or as a target for cancer prevention strategies.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and poses significant threats to individuals with diabetes. The concept of gut-kidney axis has gained increasing attention in recent years and the in the occurrence and development of DN, alterations in the gut microbiota also plays a crucial and indispensable role. However, the specific causal relationships between various gut microbial communities and DN, as well as the underlying molecular mechanisms, remains unclear. This study utilized data from genome-wide association studies. After screening for qualified instrumental variables, mendelian randomization causal analyses were performed by inverse variance weighting, MR-Egger, weighted median, weighted mode and MR-RAPS methods. Additionally, sensitivity analyses such as heterogeneity, multiplicity, and the direction of the causal effect were carried out to ensure that the results were robust. After identifying significant gut microbiota, protein-proteomics mediation analysis was conducted on potential 3282 plasma proteins to determine those with mediating effects. Finally, Reactome enrichment analysis was performed to ascertain metabolic or signaling pathways with mediating effects. Mendelian randomization analysis indicated associations between 21 gut microbiota and DN. After adjusting significance levels, Catenibacterium and Parasutterella were found to have causal effects on the onset of DN. Subsequently, we identified 22 plasma proteins with mediating effects, along with 27 metabolic or signaling pathways including activated propionic acid metabolism. Increased in the abundance of Catenibacterium and Parasutterella intestinal bacteria are causative factors for DN. More importantly, the underlying mechanism by which the increased abundance of Catenibacterium and Parasutterella intestinal bacteria lead to DN were revealed, providing a blueprint for the involvement of gut-kidney axis in the pathogenesis of DN and paving the way for future studies.

This study reports trends in acute glomerulonephritis (AGN) mortality in older adults (aged 65-94 years) and its association with age, period, and birth cohort across 204 countries and territories over the past 30 years, using data from the Global Burden of Disease (GBD) 2021 Study. An age-period-cohort model was used to estimate the overall annual percentage change in AGN mortality (net drift), annual percentage change for individuals aged 65-94 years (local drift), and longitudinal age-specific rates adjusted for period bias and period/cohort relative risks from 1992 to 2021. In 2021, there were 6213 AGN-related deaths globally (95% UI: 4460-7961). Between 1992 and 2021, the net drift for AGN mortality in high socio-demographic index (SDI) countries was 3.15% per year (95% CI 2.62-3.69), compared to - 1.18% per year in low SDI countries (95% CI - 2.01 to - 0.33). High-middle SDI countries had a decline of - 1.49% per year (95% CI - 1.80 to - 1.18), middle SDI countries - 1.52% per year (95% CI - 1.75 to - 1.28), and low-middle SDI countries - 1.78% per year (95% CI - 2.37 to - 1.20). Globally, high SDI countries showed an upward trend in AGN mortality, while others showed a downward trend. Despite the declining mortality in many regions, 15 high SDI countries, 5 high-middle SDI countries, 4 middle SDI countries, 5 low-middle SDI countries, and 3 low SDI countries showed poor or worsening outcomes in the most recent period and birth cohort. These findings suggest that AGN mortality trends are not related to a country's economic development, highlighting the need for high SDI countries to invest more in AGN-related healthcare.

The simultaneous occurrence of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and light chain proximal tubulopathy (LCPT) presents a unique diagnostic and therapeutic challenge. PGNMID is characterized by monoclonal immunoglobulin deposition in glomeruli, leading to proliferative glomerular pathology, while LCPT involves monoclonal light chain deposition in proximal tubular cells, causing tubulointerstitial damage. Both conditions are classified under monoclonal gammopathy of renal significance (MGRS), but their coexistence in a single patient is exceedingly rare. This case report details the presentation of a patient with nephrotic syndrome and renal insufficiency, where renal biopsy revealed both PGNMID and LCPT. Treatment with bortezomib, cyclophosphamide, and dexamethasone achieved clinical remission and significant renal function recovery. This case emphasizes the critical role of renal biopsy in the diagnosis, particularly in the absence of detectable monoclonal proteins, and demonstrates the efficacy of targeted therapy in managing such complex renal pathologies. These findings contribute to a better understanding of MGRS and may guide future therapeutic strategies for similar cases.

RATIONALE:Immunotactoid glomerulopathy (ITG) is a rare glomerular disease characterized by protein deposition in hollow microtubules on electron microscopy. Patients may present with proteinuria, hematuria, hypertension, and renal insufficiency, and some patients even progress to end-stage renal disease (ESRD). In patients with ESRD, ITG recurs in more than 50% of patients after kidney transplantation; however, there is no clear treatment plan for these patients owing to the limited number of reported cases. PATIENT CONCERNS:In this study, we report a case of a 58-year-old male who was admitted to our hospital with elevated blood creatinine with proteinuria. DIAGNOSES:Renal biopsy suggested membranoproliferative glomerulonephritis with findings suggestive of ITG on electron microscopy. INTERVENTIONS:After the first diagnosis of renal insufficiency, the patient was treated with rituximab; however, the patient's symptoms did not improve, and blood creatinine continued to increase. The patient progressed to ESRD, and 3 years later, kidney transplantation was performed. After surgery, he was regularly treated with tacrolimus, mycophenolate mofetil, and prednisone acetate for antirejection. Five months after surgery, a renal biopsy was performed again due to proteinuria, and the results suggested ITG recurrence. The patient's blood CD19-positive B-cell count was 0. Therefore, he was not administered rituximab again. OUTCOMES:The patient is now under regular review; his blood creatinine is relatively stable (120-150 mmol/L), while his 24-hour urine protein quantification is higher than the normal range. LESSONS:This study expands the number of reported cases of this condition and will be useful to better understand the treatment options for patients with ITG recurrence after kidney transplantation.

Background Lupus nephritis (LN) emerges as a severe complication of systemic lupus erythematosus (SLE), significantly affecting patient survival. Despite improvements in treatment reducing LN’s morbidity and mortality, existing therapies remain suboptimal, emphasizing the necessity for early detection to improve patient outcomes.Methods This study employs bioinformatics and machine learning to identify and validate potential LN biomarkers using immunohistochemistry (IHC). It explores the relationship between these biomarkers and the clinical and pathological characteristics of LN, assessing their prognostic significance. The research provides deeper mechanistic insights by employing Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the study characterizes the immune profiles of LN patients through the CIBERSORT algorithm, focusing on the role of interferon-inducible protein 44 (IFI44) as a key biomarker.Results IFI44 shows elevated expression in LN-affected kidneys, compared to healthy controls. The levels of IFI44 positively correlate with serum creatinine and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and inversely with serum complement C3 and initial estimated glomerular filtration rate (eGFR).Conclusion IFI44 is identified as a promising biomarker for LN, offering potential to refine the assessment of disease progression and predict clinical outcomes. This facilitates the development of more personalized treatment strategies for LN patients.

IntroductionIgA nephropathy (IgAN), a prevalent form of glomerulonephritis globally, exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various physiological and pathological processes, including renal conditions. Prior observational studies have suggested a potential link between cathepsins and IgAN, yet the precise causal relationship remains unclear.MethodsWe conducted a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data to explore the causal association between cathepsins and IgAN systematically. Additionally, immunohistochemical (IHC) staining and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. We investigated the underlying mechanisms via gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Molecular docking and virtual screening were also performed to identify potential drug candidates through drug repositioning.ResultsUnivariate MR analyses demonstrated a significant link between increased cathepsin S (CTSS) levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041 (95% CI=1.009–1.073, P=0.012) as estimated using the inverse variance weighting (IVW) method. In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels continued to show a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037, 95% CI=1.006–1.069). However, reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins. IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis. Investigations into immune cell infiltration, GSEA, and GSVA highlighted the role of CTSS expression in the immune dysregulation observed in IgAN. Molecular docking and virtual screening pinpointed Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS.ConclusionElevated CTSS levels are associated with an increased risk of IgAN, and this enzyme is notably overexpressed in IgAN patients’ serum and renal tissues. CTSS could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating IgAN.

Renal fibrosis, specifically tubulointerstitial fibrosis, represents the predominant pathological consequence observed in the context of progressive chronic kidney conditions. The pathogenesis of renal fibrosis encompasses a multifaceted interplay of mechanisms, including but not limited to interstitial fibroblast proliferation, activation, augmented production of extracellular matrix (ECM) components, and impaired ECM degradation. Notably, mitochondria, the intracellular organelles responsible for orchestrating biological oxidation processes in mammalian cells, assume a pivotal role within this intricate milieu. Mitochondrial dysfunction, when manifest, can incite a cascade of events, including inflammatory responses, perturbed mitochondrial autophagy, and associated processes, ultimately culminating in the genesis of renal fibrosis. This comprehensive review endeavors to furnish an exegesis of mitochondrial pathophysiology and biogenesis, elucidating the precise mechanisms through which mitochondrial aberrations contribute to the onset and progression of renal fibrosis. We explored how mitochondrial dysfunction, mitochondrial cytopathy and mitochondrial autophagy mediate ECM deposition and renal fibrosis from a multicellular perspective of mesangial cells, endothelial cells, podocytes, macrophages and fibroblasts. Furthermore, it succinctly encapsulates the most recent advancements in the realm of mitochondrial-targeted therapeutic strategies aimed at mitigating renal fibrosis.

RationaleMonoclonal gammopathy of renal significance (MGRS) represents a group of disorders caused by monoclonal immunoglobulin (M protein) secreted by B cells or plasma cells. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) is a glomerular disease and a form of MGRS. Here, we presented a rare case of a patient with IgM kappa PGNMID complicated with nocardiosis dermatitis.Patient concerns and diagnosesA 56-year-old man was admitted to the hospital because of cutaneous purpura and proteinuria. His initial pathological diagnosis indicated membranous proliferative glomerulonephritis, IgM(++), and subacute interstitial nephritis. Based on further examination, he was finally diagnosed to have IgM kappa PGNMID and subacute interstitial nephritis. After the initial diagnosis, the patient received hormonal therapy. During the treatment, nocardiosis dermatitis emerged as a complication, and the hormonal therapy was gradually reduced. The patient refused further treatment with rituximab, and his health is currently stable.OutcomesIgM kappa PGNMID complicated with nocardiosis dermatitis is an extremely rare occurrence. Laboratory examination and pathological analysis are required to confirm the diagnosis of this disorder. Timely and accurate diagnosis is essential for the appropriate treatment of PGNMID.

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid β-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.

Postoperative JC viruria is common in kidney transplant recipients, however there remains a dearth of research on perioperative JCV infection in this population. The clinical significance of JCV monitoring in kidney transplant recipients remains unclear. Based on JCV urine monitoring during the perioperative phase, renal transplant recipients who underwent perioperative and postoperative monitoring at our center were categorized into two groups: the perioperative JC virus infection group and the control group consisting of recipients without detectable JCV DNA in plasma or urine during the two-year follow-up period. A comparative analysis of baseline data was initially performed, followed by a 1:1 propensity score matching of 80 cases from each group. Within the first month after transplantation, the JC viruria group exhibited a significant decrease in the incidence of delayed graft function compared to the control group (P = 0.031).Over the two-year postoperative period, the JC viruria group displayed a significantly lower rate of acute rejection (P = 0.027). Notably, the JC viruria group demonstrated higher estimated glomerular filtration rate levels compared to the control group, particularly within the first year post-transplantation. Moreover, recipient and transplant kidney survival rates did not significantly differ between the two groups (P = 0.642). Perioperative JC viruria in kidney transplant recipients may persist beyond the initial two postoperative years. The presence of JCV is associated with lower rates of DGF and acute rejection, indicating a favorable post-transplant recovery. These findings provide novel insights into the importance of postoperative JCV monitoring.

BackgroundPatients with diabetic kidney disease (DKD) often have gastrointestinal dysfunction such as inflammatory bowel disease (IBD). This study aims to investigate the genetic mechanism leading to IBD in DKD patients through data mining and bioinformatics analysis.MethodsThe disease-related genes of DKD and IBD were searched from the five databases of OMIM, GeneCards, PharmGkb, TTD, and DrugBank, and the intersection part of the two diseases were taken to obtain the risk genes of DKD complicated with IBD. A protein–protein interaction (PPI) network analysis was performed on risk genes, and three topological parameters of degree, betweenness, and closeness of nodes in the network were used to identify key risk genes. Finally, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the risk genes to explore the related mechanism of DKD merging IBD.ResultsThis study identified 495 risk genes for DKD complicated with IBD. After constructing a protein–protein interaction network and screening for three times, six key risk genes were obtained, including matrix metalloproteinase 2 (MMP2), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2), interleukin (IL)-18, IL-13, and C–C motif chemokine ligand 5 (CCL5). Based on GO enrichment analysis, we found that DKD genes complicated with IBD were associated with 3,646 biological processes such as inflammatory response regulation, 121 cellular components such as cytoplasmic vesicles, and 276 molecular functions such as G-protein-coupled receptor binding. Based on KEGG enrichment analysis, we found that the risk genes of DKD combined with IBD were associated with 181 pathways, such as the PI3K-Akt signaling pathway, advanced glycation end product–receptor for AGE (AGE-RAGE) signaling pathway and hypoxia-inducible factor (HIF)-1 signaling pathway.ConclusionThere is a genetic mechanism for the complication of IBD in patients with CKD. Oxidative stress, chronic inflammatory response, and immune dysfunction were possible mechanisms for DKD complicated with IBD.

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.

BACKGROUND:Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). However, the current management of LN remains unsatisfactory due to sneaky symptoms during early stages and lack of reliable predictors of disease progression.METHODS:Bioinformatics and machine learning algorithms were initially used to explore the potential biomarkers for LN development. Identified biomarker expression was evaluated by immunohistochemistry (IHC) and multiplex immunofluorescence (IF) in 104 LN patients, 12 diabetic kidney disease (DKD) patients, 12 minimal change disease (MCD) patients, 12 IgA nephropathy (IgAN) patients and 14 normal controls (NC). The association of biomarker expression with clinicopathologic indices and prognosis was analyzed. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were utilized to explore potential mechanisms.RESULTS:Interferon-inducible protein 16 (IFI16) was identified as a potential biomarker for LN. IFI16 was highly expressed in the kidneys of LN patients compared to those with MCD, DKD, IgAN or NC. IFI16 co-localized with certain renal and inflammatory cells. Glomerular IFI16 expression was correlated with pathological activity indices of LN, while tubulointerstitial IFI16 expression was correlated with pathological chronicity indices. Renal IFI16 expression was positively associated with systemic lupus erythematosus disease activity index (SLEDAI) and serum creatinine while negatively related to baseline eGFR and serum complement C3. Additionally, higher IFI16 expression was closely related to poorer prognosis of LN patients. GSEA and GSVA suggested that IFI16 expression was involved in adaptive immune-related processes of LN.CONCLUSION:Renal IFI16 expression is a potential biomarker for disease activity and clinical prognosis in LN patients. Renal IFI16 levels may be used to shed light on predicting the renal response and develop precise therapy for LN.

Background:Systemic lupus erythematosus (SLE), a multisystemic autoimmune disease, is very aggressive in pediatric-onset patients as they are prone to develop lupus nephritis (LN). Although renal C4d positivity is correlated with the activity of renal disease and SLE in adult-onset LN patients, available information for pediatric-onset patients is limited.Methods:To evaluate the potential diagnostic significance of renal C4d staining in pediatric LN patients, we retrospectively detected C4d staining by immunohistochemistry on renal biopsy specimens from 58 pediatric LN patients. The clinical and laboratory data at the time of the kidney biopsy and the renal disease activity of histological injury were analyzed according to the C4d staining status.Results:Glomerular C4d (G-C4d)-positive staining was detected in all 58 cases of LN. Patients with a G-C4d score of 2 displayed more severe proteinuria than those with a G-C4d score of 1 (24-h urinary protein: 3.40 ± 3.55 g vs. 1.36 ± 1.24 g, P < 0.05). Peritubular capillary C4d (PTC-C4d) positivity was found in 34 of 58 LN patients (58.62%). The PTC-C4d-positive patient groups (patients with a PTC-C4d score of 1 or 2) had higher serum creatinine and blood urea nitrogen levels as well as renal pathological activity index (AI) and SLE disease activity index (SLEDAI) scores; however, they had lower serum complement C3 and C4 levels compared to PTC-C4d-negative patients (P < 0.05). In addition, there was positive tubular basement membrane C4d (TBM-C4d) staining in 11 of 58 LN patients (18.96%), and a higher proportion of TBM-C4d-positive patients than TBM-C4d-negative patients (63.63% vs. 21.27%) had hypertension.Conclusion:Our study revealed that G-C4d, PTC-C4d, and TMB-C4d were positively correlated with proteinuria, disease activity and severity, and hypertension, respectively, in pediatric LN patients. These data suggest that renal C4d is a potential biomarker for disease activity and severity in pediatric LN patients, providing insights into the development of novel identification and therapeutic approaches for pediatric-onset SLE with LN.

Rationale: The causal relationship between anti-glomerular basement membrane (anti-GBM) disease and immunoglobulin A (IgA) nephropathy is still unclear and cases of concurrent anti-GBM disease and IgA nephropathy are very rare, especially with a good prognosis and long-term follow-up. Here, we report a case of concurrent anti-GBM disease and IgA nephropathy. By using corticosteroids and cyclophosphamide in combination with plasmapheresis, the patient achieved a very good prognosis with complete normalization of renal function and complete disappearance of hematuria and proteinuria at the subsequent follow-up. To our knowledge, no previous case with such a long follow-up and such a good prognosis have been reported. Patient concerns: This case report describes a 26-year-old Chinese woman who presented with fever as the initial symptom, followed by dysmorphic hematuria, overt proteinuria and rapidly worsening renal function. Before admission, the patient received symptomatic supportive treatment such as intravenous albumin infusion, improvement of circulation, but the symptoms were not significantly improved. Diagnosis: Per the results of kidney biopsy, the patient was diagnosed with crescentic glomerulonephritis and anti-GBM disease with IgA nephropathy. Interventions: The key to obtain a good prognosis was the early application of corticosteroids and cyclophosphamide in combination with plasmapheresis to make the anti-GBM antibody turn negative quickly. Outcomes: After 2 weeks of therapy, the patients' anti-GBM antibody turned negative and serum creatinine improved to a normal range. After 10 months, the patient's proteinuria level reached complete remission. After 12 months, the patient's hematuria had disappeared completely. Lessons: This case provides experience in the treatment of concurrent anti-GBM disease and IgA nephropathy and highlights the importance of early application of plasmapheresis and immunosuppressive therapy to obtain a good prognosis.