Objective To explore the associated factors for membranous nephropathy (MN) patients with IgM deposition, and to construct a prediction model. Methods This study was a retrospective cohort study. Patients diagnosed with MN with IgM deposition by renal biopsy in the Fourth Hospital of Hebei Medical University from February 2017 to December 2023 were retrospectively included. Clinical and pathological data were collected. The study population was randomized into a training set and a validation set at a 7:3 ratio. The endpoint event was defined as the remission of MN, and the patients were divided into remission group and non-remission group to compare the clinical and pathological examination results. Least absolute shrinkage and selection operator regression analysis and Cox regression analysis were used to explore the associated factors of poor prognosis of MN patients with IgM deposition. Internal validation was conducted using the validation set data. The clinical efficacy of the predictive model was evaluated by calculating the area under the receiver operating characteristic (ROC) curve and generating calibration curves. The total nomogram score for each patient was calculated based on the training set data, and the predictive performance was assessed by plotting the ROC curve. Patients were then stratified into low-risk and high-risk groups according to the optimal cut-off value derived from the ROC analysis of the total nomogram score. Kaplan-Meier survival analysis was performed to compare the remission rate between the two groups. Model performance was evaluated using the validation set. Results A total of 200 MN patients with IgM deposition were included, and 49.0% of them achieved clinical remission. In the training set, statistically significant differences were observed in 24-hour urine protein quantification (Z=-2.638, P=0.008), renal arteriolar wall thickening (χ2=6.891, P=0.009), the proportion of patients receiving immunosuppressive therapy (χ2=21.381, P<0.001), and the proportion of patients treated with corticosteroids combined with cyclophosphamide (χ2=10.107, P=0.001). Through least absolute shrinkage and selection operator regression and Cox regression, 2 factors associated with clinical remission in MN patients with IgM deposition were simultaneously identified from 16 potential associated factors, including the use of immunosuppressants (HR=3.823, 95% CI 2.055-7.113, P<0.001), and renal arteriolar wall thickening (HR=0.428, 95% CI 0.221-0.831, P=0.012). Incorporating the clinical measurement of phospholipase A2 receptor (PLA2R) antibodies, a predictive model was established. The performance of the model was evaluated using the training dataset, yielding an area under the ROC curve of 0.731 (95% CI 0.648-0.814), with a sensitivity of 88.7% and a specificity of 55.1%. The optimal cut-off value was a total nomogram score of 41.7 points. The Kaplan-Meier survival analysis showed that the remission rate was significantly higher in the low-risk group than that of the high-risk group (Log-rank test, χ2=33.525, P<0.001). Model validation was performed using the validation dataset, which showed an AUC of 0.715 (95% CI 0.591-0.839), sensitivity of 70.4%, and specificity of 63.6%. Similarly, the Kaplan-Meier survival analysis demonstrated a significantly higher remission rate in the low-risk group than in the high-risk group (Log-rank test, χ2=8.467, P=0.004). Conclusion A nomogram predictive model for remission of MN patients with IgM deposition, based on serum PLA2R antibody levels, the use of immunosuppressive therapy, and renal arteriolar wall thickening is developed. The model demonstrates a moderate clinical applicability.

Objective To investigate the association between serum IgG concentration and renal prognosis in patients with IgA nephropathy (IgAN). Methods It was a multi-center retrospective cohort study, patients with biopsy proven primary IgAN who were recorded in the Chinese IgA Nephropathy Information Registration System between April 1996 and September 2018 were included. Exclusion criteria were: (1) age <18 years; (2) <8 glomeruli in biopsy specimens; (3) estimated glomerular filtration rate (eGFR) <15 ml·min^-1·(1.73 m²)^-1 at biopsy; (4) missing baseline serum IgG values; (5) incomplete follow-up data; (6) follow-up duration <12 months. Enrolled patients were divided into 3 groups according to the baseline tertiles of serum IgG: ≤9.50 g/L (G1 group), 9.51-11.99 g/L (G2 group), and ≥12.00 g/L (G3 group). Clinical, and pathological parameters were compared across groups. The endpoint events were defined as doubled serum creatinine level from baseline, or end-stage renal disease (ESRD). Results A total of 1 976 IgAN patients were included in this study, 631 were in G1 group, 664 in G2 group, and 681 in G3 group. The comparison of baseline clinical data showed that there were statistically significant differences among the three groups in terms of gender, age, microscopic hematuria, edema, body mass index, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, blood uric acid, blood albumin, serum IgA, serum IgM, the proportion of using immunosuppressants, and the proportion of using glucocorticoids (all P<0.05). In terms of pathology, the higher the serum IgG concentration, the relatively less severe the overall renal pathological damage. The results of univariate Cox regression analysis showed that gender, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, total protein, serum albumin, globulin, serum IgG, Oxford renal pathological classification, glomerular sclerosis ratio, and glomerular IgM deposition were all associated with the occurrence of renal endpoint events (all P<0.05). Based on clinical practice and previous studies, after adjusting for gender, age, systolic blood pressure, diastolic blood pressure, eGFR, 24-hour urine protein quantity, body mass index, Oxford renal pathological classification, glomerular sclerosis ratio, and the use of renin-angiotensin-aldosterone system inhibitors, glucocorticoids, and immunosuppressants, multivariate Cox regression analysis showed that as a continuous variable, the baseline serum IgG level (HR=0.91, 95% CI 0.87-0.96) was independently associated with the risk of renal endpoint events in IgAN patients; as a categorical variable, with serum IgG ≤ 9.50 g/L as the reference, serum IgG 9.51-11.99 g/L and serum IgG ≥ 12.00 g/L were independent factors for the occurrence of renal endpoint events in IgAN patients (HR=0.69, 95% CI 0.49-0.96, P=0.027; HR=0.50, 95% CI 0.34-0.74, P<0.001). During a median follow-up of 33(21, 53) months started from the date of renal biopsy and continued until December 31, 2019, the median follow-up duration was 33 (21, 53) months, and a total of 232 patients (11.74%) reached the composite endpoint. Kaplan-Meier survival analysis showed that the higher the serum IgG concentration in patients with IgAN, the higher their cumulative renal survival rate (Log-rank test, χ²=47.176, P<0.001). Conclusion The higher level of serum IgG at diagnosis is associated with better clinicopathologic features and renal outcomes, and may portend better renal survival in IgAN patients.

Objective To investigate the risk factors associated with 90-day mortality in critically ill patients receiving continuous renal replacement therapy (CRRT), with a particular focus on the association between hypotension within the first hour of CRRT initiation and 90-day mortality after hospital admission. Methods This study was a post hoc analysis of a prospective cohort study investigating the impact of colloid versus crystalloid priming solutions on early hemodynamics in critically ill patients undergoing CRRT. The study enrolled intensive care unit patients who received CRRT at West China Hospital of Sichuan University from January 2024 to May 2024. The data were collected including demographic characteristics, laboratory tests, CRRT-related parameters, blood pressure, heart rate, sequential organ failure assessment scores, and vasoactive-inotropic score, etc. The 90-day survival outcome after hospital admission of critically ill patients aged 18-80 years who received continuous veno-venous hemodiafiltration was used as the primary outcome indicator. A Cox proportional hazards model analysis was conducted, and the predictive ability of the model was evaluated along with the test of the proportional hazards assumption. The risk factors associated with the 90-day mortality after hospital admission of critically ill patients receiving CRRT were explored, with a particular focus on whether hypotension occurring within the first hour of CRRT initiation was one of these risk factors. Results A total of 208 patients were included in this study. Within 90 days after hospital admission, 141 patients (67.8%) died, among whom 102 were male (72.3%) and the median age was 61.0 (50.0, 71.5) years; 67 patients (32.2%) survived, among whom 53 were males (79.1%) and the median age was 56.0 (47.0, 68.0) years. The incidence of hypotension within the first hour of CRRT initiation was significantly higher in the death group than in the survival group [29.8% (42/141) vs. 16.4% (11/67), χ²=4.275, P=0.039]. Moreover, The mortality rate of the group with hypotension within the first hour of CRRT initiation was higher than that of the group without hypotension [79.2% (42/53) vs. 63.9% (99/155), χ²=4.275, P=0.039]. The Kaplan-Meier survival analysis showed that the median survival time of patients without hypotension within the first hour of CRRT initiation [39.0 d (95% CI 23.2-54.8)] was longer than that of patients with hypotension [26.0 d (95% CI 18.9-33.1)], and the 90-day cumulative survival rate after hospital admission of patients without hypotension was significantly higher than that of patients with hypotension (Log-rank test, χ²=5.100, P=0.024). Univariate and multivariate Cox proportional hazards analyses demonstrated that serum albumin (HR=0.964, 95% CI 0.933-0.997, P=0.030), sequential organ failure assessment score (HR=1.064, 95% CI 1.012-1.118, P=0.015), and the use of mechanical ventilation (HR=8.272, 95% CI 1.145-59.743, P=0.036) were significantly associated with 90-day mortality in critically ill patients undergoing CRRT. In contrast, the vasoactive-inotropic score (HR=1.004, 95% CI 0.999-1.008, P=0.079) and the presence of hypotension within the first hour of CRRT initiation (HR=1.236, 95% CI 0.833-1.835, P=0.293) were not significantly associated with 90-day mortality in critically ill patients undergoing CRRT. The consistency index of this model was 0.654 (95% CI 0.617-0.691), the area under the receiver operating characteristic curve was 0.724 (95% CI 0.658-0.800), and the calibration curve showed that the predicted values of the model were well fitted to the actual observations, suggesting that the predictive effect of this model was relatively ideal. Conclusions In critically ill patients undergoing CRRT, the occurrence of hypotension within the first hour of CRRT initiation was not significantly associated with 90-day mortality after hospital admission. Lower serum albumin levels, higher sequential organ failure assessment scores, and the use of mechanical ventilation may be the risk factors for 90-day mortality in this population.

Objective To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome. Methods It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents. Results There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab. Conclusion Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Objective To explore the value of neutrophil extracellular traps (NETs) and interleukin (IL)-33 in the early diagnosis of contrast-induced acute kidney injury (CIAKI). Methods It was a prospective cohort study. The clinical data of patients who underwent coronary angiography (CAG) in Sir Run Run Hospital, Nanjing Medical University from December 2022 to December 2023 were collected. The main indicators of NETs included myeloperoxidase (MPO), neutrophil elastase (NE), citrullinated histone H3 (H3Cit) and antimicrobial peptide LL-37 amide (LL-37). Serum samples were collected before CAG, and 2 hours and 12 hours after CAG, and the levels of MPO, NE, H3Cit, LL?37, IL?33 and neutrophil gelatinase-associated lipocalin (NGAL) were detected. The differences of clinical data between CIAKI group and non-CIAKI group were compared. Multivariate logistic regression model was applied to analyze the risk factors of CIAKI. The receiver- operating characteristic curve was used to evaluate the predictive performance of biomarkers. Spearman correlation analysis was used to analyze the correlations among those biomarkers. Results A total of 280 eligible patients with CAG were included in this study, with age of (65±13) years and 203 males (72.5%). The incidence rate of CIAKI was 11.8% (33/280). Compared with non-CIAKI group, the proportions of diabetes (χ²=5.302, P=0.021), preoperative positive urine protein (χ²=6.871, P=0.009), taking beta-blockers (χ²=4.580, P=0.032), diuretics (χ²=21.987, P<0.001) and calcium channel blocker (χ²=10.424, P=0.001), preoperative blood glucose (Z=2.807, P=0.005), preoperative blood urea nitrogen (Z=2.504, P=0.012), neutrophil at 24 hours after CAG (Z=2.173, P=0.030), serum creatinine at 24 hours after CAG (Z=4.000, P<0.001), and blood urea nitrogen at 24 hours after CAG (Z=4.459, P<0.001) were higher, while the preoperative hemoglobin (Z=-2.380, P=0.017) and serum albumin (Z=-2.556, P=0.011) were lower in CIAKI group. Multivariate logistic regression analysis showed that increasing neutrophil at 24 hours after CAG (OR=1.180， 95% CI 1.037-1.341), diuretics (OR=5.615，95% CI 2.294-13.745) and calcium channel blockers (OR=3.141，95% CI 1.374-7.182) were independent influencing factors of CIAKI. There were statistically significant differences in the levels of serum NE, MPO, H3Cit, LL-37, NGAL and IL-33 among before CAG, 2 hours after CAG and 12 hours after CAG in the overall population, CIAKI group and non-CIAKI group (all P<0.05). In addition, the changes of IL?33 before CAG and 12 hours after CAG was positively correlated with the changes of MPO, NE, H3Cit, LL?37, NGAL, serum creatinine and blood urea nitrogen before CAG and 12 hours after CAG (all P<0.05). The levels of NE (Z=3.435, P=0.001; Z=6.164， P<0.001), MPO (Z=3.627, P<0.001; Z=4.729, P<0.001), H3Cit (Z=5.174, P<0.001; Z=6.241, P<0.001), LL?37 (Z=4.986, P<0.001; Z=6.346, P<0.001), NGAL (Z=2.956, P=0.003; Z=4.263, P<0.001) and IL?33 (Z=5.056, P<0.001; Z=6.240, P<0.001) in CIAKI group at 2 h and 12 h after CAG were significantly higher than those in non-CIAKI group. The receiver-operating characteristic curve indicated that the combined AUC of neutrophil 24 hours after CAG, diuretics and calcium channel blockers in predicting CIAKI was 0.791. NE (AUC=0.701), MPO (AUC=0.712), H3Cit (AUC=0.777), LL-37 (AUC=0.767) and IL-33 (AUC=0.795) at 2 hours after CAG predicted CIAKI relatively well. NE (AUC=0.865), MPO (AUC=0.758), H3Cit (AUC=0.834), LL?37 (AUC=0.840) and IL?33 (AUC=0.867) at 12 hours after CAG had better prediction effect for CIAKI. The AUC of NETs combined with IL?33 in predicting CIAKI at 2 hours and 12 hours after CAG was 0.874 and 0.956, respectively. Conclusions CIAKI patients exhibit elevated levels of NETs and IL?33. Serum MPO, NE, H3Cit, LL?37 and IL?33 at 12 hours after CAG can predict the occurrence of CIAKI. The combination of NETs and IL?33 is more effective in predicting CIAKI.

Objective To investigate the therapeutic effect of faecal microbiota transplantation (FMT) on IgA nephropathy (IgAN) in rats and the potential mechanisms. Methods Eighteen 6-week-old female Sprague-Dawley rats were divided into three groups by random number table method: the control group, IgAN group and IgAN+FMT group. IgAN models were established in the IgAN and IgAN+FMT groups using bovine serum albumin, a 5∶1 mixture of castor oil and carbon tetrachloride, and lipopolysaccharide. The control group received equivalent volume of distilled water or 0.9% sodium chloride solution. The IgAN+FMT group underwent FMT via enema with microbiota derived from control group rats. Both the control and IgAN groups received equivalent 0.9% sodium chloride solution via enema. After the intervention was completed, at the end of the experiment, the urine of rats was collected. Rats were then euthanized via intraperitoneal injection of 2% pentobarbital (100 mg/kg) for collection of renal and ileal tissues. Changes in urinary red blood cells were observed under a light microscope and the protein levels were detected. HE staining, PAS staining and immunofluorescence were employed to observe the effects of FMT on the kidney tissues and intestinal tissues of IgAN rats. Microbiome analysis was used to evaluate the impact of FMT on the gut microbiota of IgAN rats. α diversity analysis was used to assess the community diversity of individual sample. β diversity analysis was performed using principal coordinates analysis (PCoA) and non-metric multidimensional scaling (NMDS) to assess community differences between groups. Results Compared with the control group, the IgAN group exhibited significantly higher urinary red blood cell count and protein level (both P<0.05). In comparison with the IgAN group, the IgAN+FMT group showed markedly lower urinary red blood cell count and protein level (both P<0.05), suggesting that IgAN model was successfully constructed and FMT had a certain effect on reducing urine protein in IgAN rats. HE and PAS staining revealed normal glomerular and tubular structures in control group, whereas the IgAN group exhibited mesangial hyperplasia, increased mesangial matrix, thickened tubular basement membrane, and arcuate deep-staining substances in the mesangial and paramesangial areas. After FMT intervention, these symptoms were alleviated. Immunofluorescence showed that compared with control group, IgAN group demonstrated diffuse IgA deposition in glomeruli, while IgAN+FMT group showed significantly weaker IgA deposition intensity than IgAN group (both P<0.05). Intestinal HE staining showed intact architecture without inflammatory in controls, but structural damage, glandular distortion, goblet cell lost, and inflammatory infiltration in the IgAN group. After FMT treatment, the intestinal wall structure in the rats improved, the degree of glandular distortion decreased, and only a small number of inflammatory cells infiltrated. In the α diversity analysis, control group rats exhibited higher community diversity, IgAN group showed lower community diversity, while some samples in IgAN+FMT group displayed increased species richness and evenness. In the β diversity analysis, non-metric multidimensional scaling showed that there was a significant separation among different groups of samples, suggesting that there were significant differences in the composition of microbial communities. The stress values were all less than 0.2, confirming that the results had high reliability and could effectively reflect the relative differences among groups. Conclusion FMT can alleviate the pathological damage of intestinal and renal tissues in IgAN model rats, and reduce the deposition of IgA in renal tissues and the levels of urinary red blood cells and protein. FMT may exert a therapeutic effect by regulating the structure of intestinal microbial community.

This paper presents a rare case of renal amyloidosis complicated with primary minimal change disease. The patient initially presented with edema and proteinuria, accompanied by IgG-λ monoclonal immunoglobulinemia, leading to a diagnosis of primary systemic immunoglobulin light chain amyloidosis with renal involvement. Following treatment, the patient achieved both hematologic and renal remission. However, a renal relapse occurred two years later, presenting as nephrotic syndrome without hematologic disease recurrence. A repeat renal biopsy revealed no obvious change in amyloid deposition, but demonstrated markedly enlarged effacement of podocyte foot processes. Based on these findings, a secondary diagnosis of primary minimal change disease was established. The patient exhibited a rapid response to immunosuppressive therapy, achieving sustained long-term remission. This case underscores the importance of remaining vigilant to etiological changes in the treatment of renal diseases and highlights the role of repeated renal biopsy in refining the diagnosis and guiding treatment.

TAFRO syndrome is an idiopathic systemic inflammatory disease that overlaps with idiopathic multicentric Castleman disease (iMCD). The clinical features of TAFRO syndrome include thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis/renal insufficiency (R) and organomegaly (O). The paper reports a special clinical subtype of iMCD—TAFRO syndrome in a patient, manifested as multiple-system involvement including serous effusion (ascites), fever, thrombocytopenia, anemia, multiple lymphadenopathies, pancreatitis and renal insufficiency. Bone marrow biopsy pathology showed active bone marrow hyperplasia. Renal biopsy revealed renal thrombotic microangiopathy, acute renal tubular interstitial injury combined with chronic lesions. Lymph node biopsy demonstrated lymphoproliferative lesions consistent with Castleman disease (hyaline vascular type). Following diagnosis, glucocorticoids, tacrolimus, rituximab and lenalidomide were administered, resulting in significant symptomatic improvement: ascites disappeared, and urinary findings, erythrocyte counts, renal function and hematological indexes normalized. The paper describes the patient's clinical manifestations, diagnosis and treatment process, and prognosis, and reviews relevant literature, to improve clinicians' understanding of this rare disease.

Sodium-glucose transporter 2 (SGLT2) encoded by the SLC5A2 gene, is localized on the brush border membrane of renal proximal tubules and mediates the reabsorption of approximately 90% of glucose filtered by the glomeruli. It serves as the molecular basis for familial renal glucosuria (FRG). SGLT2 inhibitors have been widely used to treat diabetes, diabetic nephropathy, chronic kidney disease, and other conditions. The 17 kDa membrane-associated protein (MAP17) regulates SGLT2 function, and mutations in the gene encoding MAP17 can lead to FRG. Investigations into genotype-phenotype correlations in FRG patients and the structural biology of SGLT2 are critical for understanding its physiological mechanisms and pharmacological actions of SGLT2 inhibitors. This review summarizes current knowledge on genotype-phenotype relationships in FRG, advances in SGLT2 protein structure research, and MAP17-mediated regulation of SGLT2. These insights elucidate SGLT2's physiological roles and provide a theoretical foundation for optimizing clinical applications of SGLT2 inhibitors.

Chronic kidney disease (CKD)-associated pruritus (CKD?aP) is also known as uremic pruritus. It is one of the common complications in patients with end-stage renal disease. CKD?aP can occur in CKD people of all ages, with a high prevalence, seriously impairing quality of life and physical/mental health, increasing long-term mortality risk, and imposing substantial burdens on healthcare systems. It is worth noting that there is a lack of effective drugs for the treatment of CKD?aP in clinical work, and it is often overlooked by medical workers. Therefore, in order to improve clinicians' understanding of CKD?aP and provide standardized clinical practice guidance, the Expert Committee of China Special Fund for Kidney Disease Prevention and Treatment has reached this consensus on the definition, diagnostic procedures, evaluation criteria, and treatment principles of CKD?aP, aiming to provide reference for clinicians in nephrology and other related disciplines to standardize clinical diagnosis and treatment.