Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

Estrogen-responsive neural circuits governing male and female mating behavior in mice.

Decades of knockout analyses have highlighted the crucial involvement of estrogen receptors and downstream genes in controlling mating behaviors. More recently, advancements in neural circuit research have unveiled a distributed subcortical network comprising estrogen-receptor or estrogen-synthesis-enzyme-expressing cells that transforms sensory inputs into sex-specific mating actions. This review provides an overview of the latest discoveries on estrogen-responsive neurons in various brain regions and the associated neural circuits that govern different aspects of male and female mating actions in mice. By contextualizing these findings within previous knockout studies of estrogen receptors, we emphasize the emerging field of "circuit genetics", where identifying mating behavior-related neural circuits may allow for a more precise evaluation of gene functions within these circuits. Such investigations will enable a deeper understanding of how hormone fluctuation, acting through estrogen receptors and downstream genes, influences the connectivity and activity of neural circuits, ultimately impacting the manifestation of innate mating actions.

Distribution of pathological types and epidemiological characteristics based on kidney biopsy in Northwest China.

BACKGROUND: The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. METHODS: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. RESULTS: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. CONCLUSION: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

[Retrospective Analysis of the Effect of Uric Acid on the Prognosis of Immunoglobulin A Nephropathy With Stage 3-4 Chronic Kidney Disease]. / å°¿é ¸æ°´å¹³å¯¹æ ¢æ€§è‚¾è„ç— 3-4期IgAè‚¾ç— é¢„åŽå½±å“çš„å›žé¡¾æ€§åˆ†æž.

Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.

High-cutoff hemodialysis in multiple myeloma patients with acute kidney injury.

Multiple myeloma (MM), an incurable hematological malignancy with clonal proliferation of plasma cells, is mainly characterized by excessive production of monoclonal immunoglobulins and free light chains (FLCs). Kidney injury is one of the main clinical manifestations and is also a significant predictor of the prognosis of symptomatic MM patients, especially those who require dialysis-supported treatment. Overproduction of FLCs is the trigger for kidney injury, as they can induce the transcription of inflammatory and profibrotic cytokines in the proximal tubule and bind to Tamm-Horsfall protein in the distal tubules to form casts that obstruct the tubules, leading to kidney injury and even renal fibrosis. In addition to traditional antimyeloma treatment, high-cutoff hemodialysis (HCO-HD), which can effectively remove FLCs in vitro, has attracted much attention in recent years. Due to its greater membrane pore size, it has significant advantages in removing larger molecules and can be applied in rhabdomyolysis, sepsis, and even myeloma cast nephropathy. However, mounting questions have recently been raised regarding whether HCO-HD can truly provide clinical benefits in MM patients with acute kidney injury (AKI). Therefore, in this study, we discussed the pathological causes of AKI secondary to MM and summarized the current situation of HCO-HD in MM patients compared with other available extracorporeal techniques. In addition, pivotal clinical trials that reflect the ability of the clearance of FLCs and the side effects of HCO-HD are highlighted, and the relevant protocol of HCO-HD is also provided to assist clinicians in decision-making.

Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis.

Background: Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis. Methods: To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis. Results: There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis. Conclusions: For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

Probiotics, Prebiotics, and Synbiotics Improve Uremic, Inflammatory, and Gastrointestinal Symptoms in End-Stage Renal Disease With Dialysis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Probiotics, prebiotics, and synbiotics are three different supplements to treat end stage renal disease (ESRD) patients by targeting gut bacteria. The comprehensive comparison of the effectiveness of different supplements are lacking. Objectives: The purpose of this network meta-analysis (NMA) is to assess and rank the efficacy of probiotics, prebiotics, and synbiotics on inflammatory factors, uremic toxins, and gastrointestinal symptoms (GI symptoms) in ESRD patients undergoing dialysis. Methods: Randomized clinical trials were searched from the PubMed, Embase, and Cochrane Register of Controlled Trials databases, from their inception until 4 September 2021. Random-effect model were used to obtain all estimated outcomes in network meta-analysis (NMA). Effect estimates were presented as mean differences (Mean ± SD) with 95% confidence interval (CI). The comprehensive effects of all treatments were ranked by the surface under the cumulative ranking (SUCRA) probabilities. Results: Twenty-five studies involved 1,106 participants were included. Prebiotics were superior in decreasing Interleukin-6 (IL-6; SMD -0.74, 95% CI [-1.32, -0.16]) and tumor-necrosis factor-α (TNF-α; SMD -0.59, 95% CI [-1.09, -0.08]), synbiotics were more effective in declining C-reactive protein (CRP; SMD -0.69, 95% CI [-1.14, -0.24]) and endotoxin (SMD -0.83, 95% CI [-1.38, -0.27]). Regarding uremic toxins, prebiotics ranked highest in reducing indoxyl sulfate (IS; SMD -0.43, 95% CI [-0.81, -0.05]), blood urea nitrogen (BUN; SMD -0.42, 95% CI [-0.78, -0.06]), and malondialdehyde (MDA; SMD -1.88, 95% CI [-3.02, -0.75]). Probiotics were rated as best in alleviating GI symptoms (SMD: -0.52, 95% CI [-0.93, -0.1]). Conclusion: Our research indicated prebiotics were more effective in declining IL-6, TNF-α, IS, MDA, and BUN, synbiotics lowering CRP and endotoxin significantly, and probiotics were beneficial for alleviating GI symptoms, which may contribute to better clinical decisions. This study was registered in PROSPERO (Number: CRD42021277056). Systematic Review Registration: [http://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021277056].

ExoSD chips for high-purity immunomagnetic separation and high-sensitivity detection of gastric cancer cell-derived exosomes.

Gastric cancer cell-derived exosomes as biomarkers have a very high application potential to the non-invasive detection of early-stage gastric cancer. However, the small size of exosomes (30-150 nm) results in huge challenges in separating and detecting them from complex media (e.g., plasma, urine, saliva, and cell culture supernatant). Here we proposed a highly integrated exosome separation and detection (ExoSD) chip to immunomagnetic separate exosomes from cell culture supernatant in a manner of continuous flow, and to immunofluorescence detect gastric cancer cell-derived exosomes with high sensitivity. The ExoSD chip has achieved a high exosome recovery (>80%) and purity (>83%) at the injection rate of 4.8 mL/h. Furthermore, experimental results based on clinical serum samples of patients with gastric cancer (stages I and II) show that the detection rate of the ExoSD chip is as high as 70%. The proposed ExoSD chip has been successfully demonstrated as a cutting-edge platform for exosomes separation and detection. It can be served as a versatile platform to extend to the applications of separation and detection of the other cell-derived exosomes or cells.