Prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy: a retrospective study of 420 biopsy-proven cases.

BACKGROUND: This retrospective study aims to investigate the prevalence and immunopathologic characteristics of seropositive and seronegative hepatitis B virus-associated membranous nephropathy (HBV-MN). METHODS: Clinicopathologic and serologic records of 420 patients with histologically confirmed HBV-MN between January 2014 and July 2021 were examined to determine the prevalence of seropositive and seronegative HBV-MN. Serum anti-PLA2R antibody testing was conducted on 280 patients with HBV-associated membranous nephropathy (HBV-MN) from August 2018 to July 2021. Immunopathologic characteristics of HBV-MN patients and anti-PLA2R antibody positivity were analyzed. RESULTS: Among 420 pathologically confirmed HBV-MN patients, 230 (54.8%) were seropositive for HBV. The seropositive group exhibited higher blood creatinine values and incidence of liver function abnormalities than the seronegative group (p < .05). Serum anti-PLA2R antibody testing on 280 HBV-MN patients revealed a total positive rate of 44.6%, with the seronegative group showing a significantly higher rate (62.6%) compared to the seropositive group (32.1%) (p < .01). The anti-PLA2R antibody-positive group displayed higher levels of urine protein (p < .05), serum cholesterol (p < .01), and IgG4 subtypes (p < .05) compared to the negative group. Additionally, the positive group had significantly lower levels of serum albumin and IgG than the negative group (p < .01). CONCLUSIONS: This comprehensive study reveals a significantly higher prevalence of seronegative HBV-MN than previously thought. The blood creatinine values and incidence of liver function abnormalities was higher in the serology-positive group than in the serology-negative group. Notably, the seronegative group displayed a higher positive rate of anti-PLA2R antibodies compared to the seropositive group, indicating distinctive clinical and immunopathologic features.

Glucocorticoid does not improve the renal prognosis of patients with diabetic nephropathy combined with acute tubulointerstitial nephritis: a retrospective analysis.

BACKGROUND AND OBJECTIVES: In clinical practice, some patients are diagnosed with diabetic nephropathy (DN) combined with acute tubulointerstitial nephritis (ATIN) through renal biopsy. There is relatively little research on the treatment and prognosis of such patients, and no consensus exists on the use of glucocorticoid for treatment. Therefore, our study explores the progression of DN combined with ATIN and the renal outcomes after treatment with glucocorticoid. METHODS: This study retrospectively analyzed patients diagnosed with DN combined with ATIN through renal biopsy at our center from January 1, 2015, to December 31, 2021. We collected general patient information, laboratory indicators, renal pathology indicators, and the glucocorticoid usage after kidney biopsy. Follow-up data were collected from medical records. Statistical analysis methods included t-tests, non-parametric tests, and chi-square tests. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for renal endpoint events in patients. Statistical significance was defined as p-values < 0.05. RESULTS: In this study, a total of 67 patients were included. The subjects were divided into two groups based on whether they received glucocorticoid treatment: 33 patients in the steroid group and 34 in the non-steroid group. In the steroid group, 19 patients reached the renal endpoint event, which was significantly higher than in the non-steroid group (57.58% vs. 29.41%, p = 0.038). Univariate Cox regression analysis showed that serum creatinine (HR = 1.008, p < 0.001), albumin (HR = 0.919, p < 0.001), 24-h urinary protein (HR = 1.093, p = 0.002), hemoglobin (HR = 0.964, p = 0.001), triglycerides (HR = 1.12, p = 0.04), and the use of glucocorticoid (HR = 2.507, p = 0.019) were influencing factors for renal endpoint events in patients with DN combined with ATIN. Multivariate Cox regression analysis showed that albumin (HR = 0.863, p = 0.003) was an independent risk factor for renal endpoint events in patients with DN combined with ATIN. CONCLUSIONS: The use of glucocorticoid in treatment does not improve renal prognosis in patients with DN combined with ATIN. Lower levels of albumin are associated with a worse renal prognosis.

Utility of shear wave-based ultrasound elastography in chronic kidney disease and related pathological quantitative analysis.

OBJECTIVES: The purpose of this study was to investigate the effects of tissue fibrosis and microvessel density on shear wave-based ultrasound elastography (SWUE) of chronic kidney disease (CKD). In addition, we were looking to see whether SWUE could predict stage of CKD, correlating with the histology on kidney biopsy. METHODS: Renal tissue sections from 54 patients diagnosed with suspected CKD were subjected to immunohistochemistry (CD31 and CD34), and the degree of tissue fibrosis was assessed using Masson staining. Before renal puncture, both kidneys were examined using SWUE. Comparative analysis was used to assess the correlation between SWUE and microvessel density, and between SWUE and the degree of fibrosis. RESULTS: Fibrosis area according to Masson staining (p < 0.05) and integrated optical density (IOD) (p < 0.05) were positively correlated with CKD stage. The percentage of positive area (PPA) and IOD for CD31 and CD34 were not correlated with CKD stage (p > 0.05). When stage 1 CKD was removed, PPA and IOD for CD34 were negatively correlated with CKD stage (p < 0.05). Masson staining fibrosis area and IOD were not correlated with SWUE (p > 0.05), PPA and IOD for CD31 and CD34 were not correlated with SWUE (p > 0.05) and, finally, no correlation between SWUE and CKD stage was found (p > 0.05). CONCLUSION: The diagnostic value of SWUE for CKD staging was very low. The utility of SWUE in CKD was affected by many factors and its diagnostic value was limited. KEY POINTS: • There was no correlation between SWUE and the degree of fibrosis, or between SWUE and microvessel density among patients with CKD. • There was no correlation between SWUE and CKD stage and the diagnostic value of SWUE for CKD staging was very low. • The utility of SWUE in CKD is affected by many factors and its value was limited.

Efficacy and safety of low-dose rituximab as induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement: a Chinese case series.

BACKGROUND: Rituximab (RTX) is a standard therapy for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the most frequently used dose may lead to severe adverse effects (SAEs). We explored the efficacy and safety of low-dose RTX in Chinese patients with AAV. METHODS: A total of 22 Chinese patients diagnosed with AAV with renal involvement, including 8 treated with low-dose RTX (400 mg of RTX total over 4 weeks) and 14 treated with cyclophosphamide (CYC), were evaluated. The baseline clinical and pathological data and laboratory parameters during follow-up at months 1, 3, 6, and 12 were collected retrospectively. RESULTS: The baseline data showed no significant differences between the two groups. The median peripheral CD19+ cell counts in the RTX group decreased from 315.0/µL to 1.5/µL at 2 weeks, and to 2.5/µL at 1 month after the first dose. The median SCr level decreased from 267.8 µmol/L before treatment to 151.45 µmol/L at 1 month, 132.75 µmol/L at 3 months, 123.2 µmol/L at 6 months, and 151.9 µmol/L at 12 months in RTX-treated patients. The improvements in renal function, proteinuria, and ANCA titre were not significantly different between the two groups. The SAE rate was significantly lower in the RTX group (one SAE of pneumonia) compared with the CYC group. CONCLUSIONS: This is the first report that low-dose RTX could be effective for the treatment of Chinese patients with AAV with renal involvement.

Anti-glomerular basement membrane disease mediated by IgG and IgA: a case report.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is a rare autoimmune condition responsible for rapidly progressive glomerulonephritis. This disease is usually mediated by IgG autoantibodies against the noncollagenous domain of the α3(IV) collagen chain. In rare cases, IgA or IgM anti-GBM antibodies are involved. This raises the question of whether there are different types of antibody-mediated anti-GBM disease at the same time. CASE REPORT: A 37-year-old woman with anti-GBM disease mediated by IgG and IgA. The patient developed rapidly progressive glomerulonephritis with nephrotic syndrome. Indirect immunofluorescence analysis indicated the presence of IgG and IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoadsorbent assay and Western blotting as the α3(IV) collagen chain. After plasmapheresis and immunotherapy (steroids and cyclophosphamide), much improved the massive proteinuria and renal function. Follow up to date, she had normal renal function without proteinuria. CONCLUSIONS: This is the first case report of anti-GBM disease mediated by IgG and IgA. If the clinical presentation and histopathological findings are suggestive of atypical anti-GBM disease, alternative laboratory tests such as Western blotting analysis can be used to confirm the diagnosis.

Novel Model Predicts Diabetic Nephropathy in Type 2 Diabetes.

BACKGROUND: Clinical indicators for accurately distinguishing diabetic nephropathy (DN) from non-diabetic renal disease in type 2 diabetes (T2D) are lacking. This study aimed to develop and validate a nomogram for predicting DN in T2D patients with kidney disease. METHODS: A total of 302 consecutive patients with T2D who underwent renal biopsy at China-Japan Friendship Hospital between January 2014 and June 2019 were included in the study. The data were randomly split into a training set containing 70% of the patients (n = 214) and a validation set containing the remaining 30% of patients (n = 88). Multivariable logistic regression analyses were applied to develop a prediction nomogram incorporating the candidates selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using a concordance index (C-index), calibration plot, and decision curve analysis. Both internal and external validations were assessed. RESULTS: A multivariable model that included gender, diabetes duration, diabetic retinopathy, hematuria, glycated hemoglobin A1c, anemia, blood pressure, urinary protein excretion, and estimated glomerular filtration rate was represented as the nomogram. The model demonstrated very good discrimination with a C-index of 0.934 (95% CI 0.904-0.964). The calibration plot diagram of predicted probabilities against observed DN rates indicated excellent concordance. The C-index value was 0.91 for internal validation and 0.875 for external validation. Decision curve analysis demonstrated that the novel nomogram was clinically useful. CONCLUSION: The novel model was very useful for predicting DN in patients with T2D and kidney disease, and thereby could be used by clinicians either in triage or as a replacement for biopsy.

Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

Outcomes of normotensive IgA nephropathy patients with mild proteinuria who have impaired renal function.

Purpose: Typically, IgA nephropathy is a slowly progressive type of glomerulonephritis. High-grade proteinuria and hypertension are predictors of reduced kidney function. However, we found some normotensive patients with mild proteinuria could exhibit impaired renal function at the time of IgAN diagnosis. We therefore conduct a study to highlight the occurrence of these cases and to define their clinical characteristics and outcomes. Methods: The clinical, laboratory, pathological manifestations and outcomes of these IgAN patients were collected and were compared with normotensive IgA nephropathy patients with mild proteinuria and normal renal function. Patients were analyzed according to different pathological characteristics. Survival curves were constructed according to the Kaplan-Meier method. Results: Of all normotensive IgA nephropathy patients with mild proteinuria, 108 (10.1%) patients had impaired renal function. Ischemic sclerosis (79 patients) and fibrous crescent (25 patients) were the main pathological characteristics. Macroscopic hematuria (1.3%), prodromal infection (13.9%) and high serum IgA (11.4%) were significantly lower prevalences, but only proteinuria (26.6%) was more common in ischemic sclerosis group patients. Only hematuria were not found in ischemic sclerosis group and crescent group patients. The median follow-up were about 5 years. Patients in crescent group had a poor outcome compared with patients in ischemic sclerosis group. Conclusions: Some normotensive IgA nephropathy patients with mild proteinuria had impaired renal function at diagnosis. Ischemic sclerosis and fibrous crescent were the main pathological features in these patients. Patients in the crescent group had a worse outcome than patients in the ischemic sclerosis group.

US-guided Microwave Ablation of Hyperplastic Parathyroid Glands: Safety and Efficacy in Patients with End-Stage Renal Disease-A Pilot Study.

Purpose To evaluate the safety and efficacy of microwave ablation (MWA) in patients with end-stage renal disease and secondary hyperparathyroidism. Materials and Methods The study protocol was approved by the human ethics review committee. Between March 1, 2014, and June 30, 2015, 51 patients (25 men, 26 women; mean age ± standard deviation, 53.1 years ± 12.9) were enrolled. All patients had at least one enlarged parathyroid gland and secondary symptomatic hyperparathyroidism, which was treated with ultrasonographically (US) guided MWA. The levels of intact parathyroid hormone, serum calcium, phosphorus, and alkaline phosphatase were compared before and after MWA. Paired-sample t tests and paired-sample Wilcoxon signed-rank tests were used to compare treatment outcomes before and after MWA. Results Complete ablation was achieved in all 96 glands in 51 of 120 patients with severe secondary hyperparathyroidism. The mean follow-up time was 11.1 months ± 3.3. The maximum diameter of the glands ranged from 0.5 cm to 4.8 cm (mean, 1.5 cm ± 0.6). The ablation time for each gland was 216.1 seconds ± 130.1. The mean serum intact parathyroid hormone, calcium, and phosphorus levels after MWA (400 pg/mL [400 ng/L; range, 151.3-629.0 ng/L], 2.33 mmol/L ± 0.23, and 1.54 mmol/L ± 0.43, respectively) were significantly lower than those before MWA (1203 pg/mL [1203 ng/L; range, 854.7-1694.5 ng/L], 2.53 mmol/L ± 0.24, and 1.97 mmol/L ± 0.50, respectively; P < .01), while the alkaline phosphatase levels did not change with MWA (P > .05). Ipsilateral recurrent laryngeal nerve injury was seen in one patient (2%). A hematoma developed during one procedure in one patient (2%) and was treated successfully with injection of thrombin. Conclusion US-guided MWA is safe and effective for destroying parathyroid gland tissue in patients with end-stage renal disease and severe secondary hyperparathyroidism. Further experience with the technique is clearly necessary. © RSNA, 2016.

Outcomes of IgA Nephropathy with Segmental Glomerular Necrosis But without Crescent Formation.

BACKGROUND: The significance of segmental glomerular necrosis (SGN) was not evident in immunoglobulin A nephropathy (IgAN) patients. Especially, there were a number of patients who presented with slight histopathological damage except SGN. We, therefore, conducted a study to highlight the occurrence of these cases and to define their clinical characteristics and outcomes at our centre. METHODS: The clinical, laboratory and pathological manifestations and outcomes of these IgAN patients were collected and compared with IgAN patients with simily histopathological background but without SGN. Survival curves were constructed according to the Kaplan-Meier method. Multivariate Cox regression analysis was used to identify independent factors for the development of endpoint. RESULTS: Eighty-two patients with SGN but without crescents were found in Haas grades I-III. Macroscopic hematuria and prodromal infection were more popular and the mean daily proteinuria was significantly higher in patients with SGN. More patients had high serum IgA in the ecrotizing IgAN group. At last follow-up, there were no differences in hypertension, proteinuria, serum creatinine, estimated GFR and the incidence of end-point events between 2 groups. SGN was not an independent predictor for the prognosis of IgAN. Corticosteroid treatment could decrease proteinuria significantly. The outcomes of the 2 populations of necrotizing IgAN patients with or without corticosteroid treatment were not different. CONCLUSIONS: SGN can be found in mild pathological damage patients and is not always associated with crescent formation. Heavier proteinuria was found in these IgAN patients. SGN was not an independent predictor for the prognosis of IgAN.

Clinicopathological features and outcomes of IgA nephropathy with hematuria and/or minimal proteinuria.

BACKGROUND/AIMS: Information regarding the clinical and histological prognostic factors of IgA nephropathy (IgAN) is mostly derived from patients in whom diagnostic renal biopsies were performed because their proteinuria levels were higher than 1-2 g/d. The clinicopathological features and outcomes of IgAN patients presenting with normal blood pressure, normal renal function, hematuria and minimal or no proteinuria are not well described. We therefore conducted a study of the clinicopathological features and outcomes in IgAN patients with these characteristics. METHODS: The clinical, laboratory, and pathological manifestations and long-term outcomes of all IgAN patients with the above-mentioned characteristics were collected. The relationships between renal pathology, injury, long-term outcomes and clinical factors were studied, and the risk factors of IgAN were analyzed using multivariate logistic regression. RESULTS: Of all of the renal biopsy cases, IgAN with the above features accounted for 8.9%. Among these patients, 67.2% (253) showed simultaneous hematuria and proteinuria, 23.1% (87) showed only hematuria, and 9.7% (36) showed only proteinuria. Additionally, 33.8% (127) patients showed macroscopic hematuria and 65.1% (245) had a prodromal infection. Regarding renal pathological changes, 45.5% (171) of the patients were unexpectedly classified as Grade II to IV (Hass classification). Proteinuria at the time of renal biopsy was an independent predictor of more severe renal pathological injury. After a median follow-up of 75 months, 61 (16.2%) patients experienced adverse events. Among these patients, 28 (7.45%) exhibited hypertension, 22 (5.85%) presented proteinuria levels >1 g/24 h, and 11 (2.9%) developed impaired renal function. CONCLUSIONS: Severe renal histological injury may be observed in some IgAN patients with benign clinical characteristics. Proteinuria is an independent predictor of severe renal pathological injury in IgAN patients with mild proteinuria. More severe pathological injury (> Grade II, Hass classification) are predictors of poor prognosis.

Complement C3a/C3aR and C5a/C5aR deposits accelerate the progression of advanced IgA nephropathy to end-stage renal disease.

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732-0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079-9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

Unraveling the interplay of ferroptosis and immune dysregulation in diabetic kidney disease: a comprehensive molecular analysis.

BACKGROUND: Diabetic kidney disease (DKD) is a primary microvascular complication of diabetes with limited therapeutic effects. Delving into the pathogenic mechanisms of DKD and identifying new therapeutic targets is crucial. Emerging studies reveal the implication of ferroptosis and immune dysregulation in the pathogenesis of DKD, however, the precise relationship between them remains not fully elucidated. Investigating their interplay is pivotal to unraveling the pathogenesis of diabetic kidney disease, offering insights crucial for targeted interventions and improved patient outcomes. METHODS: Integrated analysis, Consensus clustering, Machine learning including Generalized Linear Models (GLM), RandomForest (RF), Support Vector Machine (SVM) and Extreme Gradient Boosting (xGB), Artificial neural network (ANN) methods of DKD glomerular mRNA sequencing were performed to screen DKD-related ferroptosis genes.CIBERSORT, ESTIMATE and ssGSEA algorithm were used to assess the infiltration of immune cells between DKD and control groups and in two distinct ferroptosis phenotypes. The ferroptosis hub genes were verified in patients with DKD and in the db/db spontaneous type 2 diabetes mouse model via immunohistochemical and Western blotting analyses in mouse podocyte MPC5 and mesangial SV40-MES-13 cells under high-glucose (HG) conditions. RESULTS: We obtained 16 differentially expressed ferroptosis related genes and patients with DKD were clustered into two subgroups by consensus clustering. Five ferroptosis genes (DUSP1,ZFP36,PDK4,CD44 and RGS4) were identified to construct a diagnostic model with a good diagnosis performance in external validation. Analysis of immune infiltration revealed immune heterogeneity between DKD patients and controls.Moreover, a notable differentiation in immune landscape, comprised of Immune cells, ESTIMATE Score, Immune Score and Stromal Score was observed between two FRG clusters. GSVA analysis indicated that autophagy, apoptosis and complement activation can participate in the regulation of ferroptosis phenotypes. Experiment results showed that ZFP36 was significantly overexpressed in both tissue and cells while CD44 was on the contrary.Meanwhile,spearman analysis showed both ZFP36 and CD44 has a strong correlation with different immune cells,especially macrophage. CONCLUSION: The regulation of the immune landscape in DKD is significantly influenced by the focal point on ferroptosis. Newly identified ferroptosis markers, CD44 and ZFP36, are poised to play essential roles through their interactions with macrophages, adding substantial value to this regulatory landscape.

Identification and validation of biomarkers in membranous nephropathy and pan-cancer analysis.

Background: Membranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive. Methods: In this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer. Results: We conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers. Conclusion: This evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.

Unraveling DDIT4 in the VDR-mTOR pathway: a novel target for drug discovery in diabetic kidney disease.

Introduction: Diabetic kidney disease (DKD) necessitates innovative therapeutic strategies. This study delves into the role of DNA damage-inducing transcription factor 4 (DDIT4) within the VDR-mTOR pathway, aiming to identify a novel target for DKD drug discovery. Methods: Transcriptome data from the Gene Expression Omnibus Database were analyzed to assess the expression of mTOR and VDR expression in human renal tissues. Clinical samples from DKD patients and minimal change disease (MCD) controls were examined, and a DKD animal model using 20-week-old db/db mice was established. DDIT4 plasmid transfection was employed to modulate the VDR-mTOR pathway, with its components evaluated using immunohistochemistry, real-time quantitative PCR (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Results: Changes in the expression of the VDR-mTOR pathway were observed in both DKD patients and the animal model. Overexpression of DDIT4 increased VDR expression and decreased levels of mTOR, p70s6k, and 4E-BP1. Furthermore, DDIT4 treatment regulated autophagy by upregulating LC3I expression and downregulating LC3II expression. Notably, DDIT4 alleviated oxidative stress by reducing the levels of lipid peroxidation product MDA, while simultaneously increasing the levels of superoxide dismutase (SOD) and glutathione (GSH), underscoring the role of DDIT4 in the pathological process of DKD and its potential as a therapeutic target. Conclusion: Unraveling DDIT4's involvement in the VDR-mTOR pathway provides insights for innovative DKD drug discovery, emphasizing its potential as a therapeutic target for future interventions.

Retroperitoneal laparoscopic renal biopsy: an 8 year experience at a single centre.

PURPOSE: To present our experience and outcome of consecutive laparoscopic renal biopsy (LRB) in a series of Chinese patients over an 8 year period. METHODS: Between January 1, 2013, and December 31, 2020, 104 patients (M/F 71/33, age 43.6 ± 16.0 years) were enrolled. All patients underwent LRB for various indications, e.g., dialysis dependence (33.7%), serum levels of creatinine ≥ 442 µmol/L (20.2%), morbid obesity (18.3%), uncontrolled severe hypertension (14.4%), aberrant renal anatomy (5.8%), solitary kidney (2.9%), deaf-mutes (2.9%), failed percutaneous biopsy (1.0%) and patient choice (1.0%). The kidney was approached via the laparoscopic retroperitoneal route using a three-port technique. Then, 16-gauge true-cut needle biopsy was performed and haemostasis was achieved by compression. Topical collagen mesh was used if necessary. RESULTS: Renal tissue was obtained in all cases. The operative time and amount of blood loss were significantly (P < 0.05) lower in 2017-2020 than 2013-2016 [42.6 ± 1.5 min and 9.6 ± 0.7 mL, respectively (n = 61) vs. 51.2 ± 1.3 min and 14.4 ± 0.9 mL, respectively (n = 43)], while the hospital stay was not significantly different between the two periods. The rate of tissue adequacy and median number of glomeruli were significantly higher in 2017-2020 than 2013-2016 [100% and 52 (IQR 24-94), respectively vs. 93% and 35 (IQR 6-98), respectively). Two postoperative complications occurred in the first 4 years: disseminated intravascular coagulation (DIC) during the operation and injury at the hilum of the kidney (n = 1 each). The renal pathological diagnoses were also complex: 70.2% of the cases were independent pathological types, including IgA nephropathy (IgAN) (13.5%), Henoch-Schönlein purpura nephritis (HSPN) (2.9%), focal segmental glomerulosclerosis (FSGS) (9.6%), membranous glomerulonephritis (MN) (1.9%), lupus nephritis (LN) (3.8%), crescentic glomerulonephritis (CreGN) (7.7%), diabetic nephropathy (DN) (10.6%), tubulointerstitial nephritis (TIN) (11.5%) and malignant hypertensive nephropathy (MHTN) (8.7%). However, the rates of combinations of two and three pathological types were 25.0% and 4.8%, respectively. CONCLUSION: Retroperitoneal LRB is a safe, reliable, minimally invasive alternative for patients in whom PRB in not feasible. As a helpful supplement to PRB, it may be necessary to use this technique more often in the future.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy: A case report.

BACKGROUND: About 70%-80% of patients with primary membranous nephropathy (MN) have phospholipase A2 receptor (PLA2R) in renal tissue. Systemic light-chain (AL) amyloidosis is the most common type of amyloidosis. MN complicated with amyloidosis is rare. CASE SUMMARY: A 48-year-old Chinese male presented with nephrotic syndrome, positive serum PLA2R antibody, and positive serum and urine IgG-lambda type M-protein, with a normal ratio of serum-free light-chain level. The patient was diagnosed with MN accompanied by AL amyloidosis. He was treated with rituximab with glucocorticoids and CyBorD regimen of chemotherapy. After 21 mo of follow-up, the patient achieved complete remission regarding nephrotic syndrome without adverse effects of chemotherapy. CONCLUSION: We report a case of PLA2R-related MN complicated with primary AL amyloidosis only with renal involvement and successfully treated with rituximab, glucocorticoids and chemotherapy.

Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients.

PURPOSE: To investigate the prognosis of patients with spontaneous remission (SR) of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). PATIENTS AND METHODS: Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021. Among them, 24 patients with SR were included in this study and follow-up. RESULTS: Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited; 11 were male, and 13 were female, with a mean age of 49.5±14.5 years (range, 30-77 years). The initial 24-hour urinary total protein and serum albumin levels were 0.29±0.14g/d and 37.5±4.4g/L, respectively, and the initial serum creatinine was 65.0±15.8µmol/L. During the follow-up of 33.9±19.1 months (range, 6-73 months), 22 (91.7%) patients maintained remission; however, one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings, and one patient experienced a repeated relapse caused by respiratory tract infection, at 50 and 70 months. A systematic review of the relevant literature was conducted, and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases. CONCLUSIONS: Most patients with SR of MN had a promising long-term prognosis, with only a few cases of relapse.

Lung cancer patients with nephropathy as the first manifestation: Literature review and clinical study report.

Background: To investigate the relationship between membranous nephropathy (MN) and lung cancer. Methods: To report patients with lung cancer detected by follow-up after the diagnosis of MN by renal biopsy in China-Japan Friendship Hospital from January 2010 to December 2019, and to study the prognosis of lung cancer-associated MN and have a review of the literature. Results: Lung cancer was detected in six patients followed for 1-27 months (median 8 months) after the diagnosis of MN: including four cases of lung adenocarcinoma, one case of carcinoma in situ, and one case of small cell lung cancer with multiple metastases. Five cases were in remission after surgical resection, and one case was remitted after chemotherapy. Six patients were negative for serum anti-PLA2R antibodies, and glomerular IgG subclass deposition detected by immunofluorescence was positive for IgG1 and IgG2. Glomerular PLA2R, THSD7A, and NELL-1 stainings were assessed in all six patients; one patient was positive for glomerular PLA2R staining, two patients were positive for glomerular THSD7A staining, and all patients were negative for NELL-1 staining. A literature review of the relationship between MN and lung cancer was performed: seven articles about cancer-associated MN were searched, reporting 32 cases of MN associated with lung cancer, among which 14 cases had nephropathy as the first manifestation and only five patients had remission of MN after treatment of lung cancer. Conclusions: A few lung cancer patients have nephropathy as the first clinical manifestation, and MN can also be remitted after treatment of lung cancer.