Recombinant human erythropoietin (rhEPO) fused with human immunoglobulin G (IgG) Fc fragment (rhEPO-Fc) is a novel erythropoiesis-stimulating agent designed to extend plasma half-life and enhance biological activity. However, data on the efficacy and safety of rhEPO-Fc in hemodialysis patients with chronic kidney disease (CKD)-related anemia remain limited. This phase 3 trial enrolled patients from 45 Chinese hospitals. Participants were randomized (2:1) to receive either rhEPO-Fc or rhEPO (Chinese hamster ovary cell-derived) for 28 weeks. The rhEPO-Fc responders were eligible for a 24-week extension period. The primary endpoint was the least square mean (LSM) change in hemoglobin (Hb) levels from baseline between weeks 21 and 28. Among 356 rhEPO-Fc and 178 rhEPO recipients, patients receiving rhEPO-Fc demonstrated non-inferiority Hb maintenance compared with rhEPO. The inter-group LSM differences in the full analysis set and per-protocol set were 3.96 g/L (95% CI: 3.02-4.89; p < 0.001) and 2.27 g/L (95% CI: 0.60-3.95; p = 0.008), respectively. Adverse drug reaction rates were comparable (rhEPO-Fc: 39.2% vs. rhEPO: 40.2%). Dose adjustments due to treatment-emergent adverse events were significantly lower with rhEPO-Fc (0.0% vs. 2.2%; p < 0.05). Deaths unrelated to the study drugs occurred in two rhEPO-Fc and four rhEPO patients. These findings indicated that rhEPO-Fc effectively maintained Hb levels in patients with CKD anemia undergoing hemodialysis, showing comparable efficacy to rhEPO with reduced dosing frequency and a similar safety profile.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPLs). B cells are known to play a crucial role in pathogenesis of APS, however, the contribution of regulatory B cells (Bregs) remains unexplored. Our study aimed to evaluate the changes of Bregs in APS patients, and further explored their potential clinical significance. We comparatively assessed and compared the changes of Bregs (defined as CD19+CD24highCD38high and CD19+CD27+CD24high) among 55 cases of APS patients (including 36 cases of pAPS patients and 19 cases of non-criteria APS patients), 44 systemic lupus erythematosus (SLE) patients, and 30 cases of healthy controls (HCs) using flow cytometry. The adjusted global antiphospholipid syndrome score (aGAPSS) was calculated for the risk stratification of APS patients. Additionally, associations of Bregs with serum aPLs status and aGAPSS were evaluated by correlation analysis or/and receiver operating characteristic (ROC) analysis. We found that APS patients exhibited significantly lower levels of CD19+CD24highCD38highBregs and CD27+CD24highBregs compared with HCs, and were significantly decreased in patients of high-risk (aGAPSS ≥ 10) compared to low-risk patients. In addition, both CD19+CD24highCD38highBregs and CD27+CD24highBregs were inversely correlated with aGAPSS. ROC curve showed that the combination of CD24highCD38highBregs and CD27+CD24highBregs improved the discriminatory performance for identifying high-risk patients (AUC = 0.753), compared with each Bregs alone. Notably, the levels of Bregs were lowest in triple positive aPLs APS patients. In subgroup analyses, a higher frequency of CD24highCD38highBregs was observed in patients with a history of thrombosis. Our results suggested that Bregs may be associated with high-risk aPL profiles and aGAPSS-based risk stratification in APS.

ObjectiveThis study aimed to investigate the effects of combining hemoperfusion (HP) with high-flux hemodialysis (HFD) on T lymphocyte subsets, mitochondrial health, and clinical outcomes in patients undergoing maintenance hemodialysis (MHD).MethodsIn this single-center, prospective, self-controlled trial, 20 MHD patients received their regular HFD treatment, with the addition of a single HP session every 2 weeks for 12 sessions. Levels of protein-bound uremic toxins (PBUTs: indoxyl sulphate [IS] and p-cresyl sulphate [PCS]), T lymphocyte subsets (CD3+, CD4+, CD8+), mitochondrial membrane potential (MMP) in T cells, and patient-reported outcomes (SF-36, PSQI, pruritus scale) were assessed before and after the 12 sessions intervention.ResultsFollowing a single HP + HFD session, IS and PCS levels decreased significantly (p < 0.001). However, their pre-perfusion levels at end were not significantly different from baseline. After 12 sessions, increases were observed in the levels of CD3+, CD4+, CD8 + cells, the CD4+/CD8 + ratio, and the percentages of CD3 + MMP, CD4 + MMP, and CD8 + MMP (all p < 0.05). Patients also demonstrated significant improvements in sleep quality (PSQI), uremic pruritus, and overall quality of life (SF-36) (all p < 0.01). Additionally, serum phosphorus and parathyroid hormone levels were significantly reduced after the treatment period.ConclusionAfter 12 sessions of combined hemoperfusion and high-flux dialysis, we observed significant increases in T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8 + ratio) and the percentage of T cells with preserved mitochondrial membrane potential. Patients also reported improved sleep quality, reduced pruritus, and better quality of life. However, pre-dialysis levels of protein-bound uremic toxins (indoxyl sulphate and p-cresyl sulphate) of last session were not significantly different from baseline, despite effective clearance immediately after each combined session. Therefore, the observed improvements in immune-related parameters cannot be mechanistically attributed to a sustained reduction in these toxins. Alternative explanations—such as intermittent attenuation of peak toxin concentrations, clearance of unmeasured solutes, or non-specific effects—remain possible. Given the single-arm, observational design, these findings are hypothesis-generating and require confirmation in randomized controlled trials.

Background Immune checkpoint inhibitors (ICIs) have improved cancer survival but increase the risk of adverse events, including acute kidney injury (AKI). Severe AKI, though rare, can disrupt treatment and worsen outcomes. Yet, research on risk factors for severe AKI in patients on PD-1/PD-L1 therapies is limited. This study aimed to identify these risk factors. Methods This retrospective cohort study analyzed electronic medical records from Zhejiang Provincial People’s Hospital from January 2019 to July 2023. In total, 907 patients who met the inclusion criteria, with a median age of 64 years, were included in the analysis. Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses were conducted to determine independent risk factors for severe AKI. Results Severe AKI was observed in 3.2% of patients with AKI, with a significantly higher mortality rate than in non-AKI patients (20.7% vs. 4.1%) during the follow-up period. Multivariate Cox regression analysis identified elevated gamma-glutamyl transferase (hazard ratio (HR): 1.17), diuretic use (HR: 3.61), nonsteroidal anti-inflammatory drug (NSAID) use (HR: 4.58), and cytotoxic drugs (HR: 5.04) as independent risk factors for severe AKI. Only 11 patients (37.5%) with severe AKI recovered. Conclusions This study highlights the importance of monitoring these factors to reduce the risk of severe AKI in patients receiving PD-1/PD-L1 antibody therapy.

BACKGROUND:This study aimed to compare uremic toxin removal with expanded hemodialysis against post-dilution online haemodiafiltration therapy in Chinese patients with chronic kidney failure in a single treatment. METHODS:This randomized, controlled, open-label, parallel, multicenter trial enrolled prevalent patients on hemodialysis. The study endpoints were to establish the non-inferiority of expanded hemodialysis versus haemodiafiltration in removing beta-2-microglobulin (β2M) and lambda-free light chains (λFLC) and to evaluate the reduction ratios of urea, alpha-1-microglobulin (α1M), myoglobin, complement factor D, kappa-free light chains (κFLC) and Chitinase-3-like protein 1 (YKL-40) during a mid-week dialysis session. The 95% confidence intervals of the difference in λFLC and β2M reduction ratios with expanded hemodialysis were compared against pre-defined non-inferiority margins (-3.783 and -7.848, respectively). Non-inferior reduction ratios were tested for superiority using hierarchical testing. RESULTS:Overall, 274 adult patients were randomized to expanded hemodialysis (n = 138) or haemodiafiltration (n = 136). No differences in demographics, baseline characteristics, and treatment parameters were observed between the arms. The reduction ratio of λFLC with expanded hemodialysis was superior to haemodiafiltration; reduction ratio difference of 17.0% [95% confidence interval: 14.8%, 19.2%]. The reduction ratio of β2M with expanded hemodialysis was non-inferior to haemodiafiltration; reduction ratio difference of -1.2% [95% confidence interval: -2.5%, 0.2%]. Expanded hemodialysis showed significantly higher removal of α1M, YKL-40, complement factor D, myoglobin, and κFLC than haemodiafiltration therapy. There were no significant differences in Kt/Vurea, urea reduction ratio, and the rate of complications between the arms. CONCLUSION:Our study demonstrates the effectiveness of expanded hemodialysis therapy in removing multiple middle molecules compared to haemodiafiltration therapy, with no observed differences in the overall safety of Chinese patients.

Abstract Acute kidney injury (AKI) is a frequent yet often overlooked complication. This study examines the incidence, unrecognized rate, and outcomes of AKI in adults at a large public Chinese hospital from 2010 to 2023. AKI rates were calculated, and outcomes were assessed using follow-up records. Multivariate logistic regression identified risk factors for unrecognized AKI. Among 2,790,540 patients, 5,080 met the AKI criteria, with an overall incidence of 0.18% (0.78% in hospitalizations, 0.05% in outpatients). The unrecognized AKI was 76.3%. In this group, 75% were stage 1, 16.7% stage 2, and 8.3% stage 3. Orthopedics had the highest unrecognized rate (94.5%) and ICUs the lowest (55.77%). Unrecognition of AKI improved from 90.3% in 2010–2011 to 70.2% in 2022–2023. AKI stage progression was linked to poorer survival. Patients with recognized AKI recovered faster than those with unrecognized AKI (8.0 vs. 9.0 days, p < 0.001). The mean follow-up time was 15.8 days, with similar rates at 28 and 90 days post-AKI for both groups. Risk factors for unrecognized AKI included lower AKI stage, baseline creatinine, absence of shock/heart disease/hypertension, and non-nephrology/surgery admissions. Non-nephrology physicians’ unfamiliarity with AKI guidelines may contribute to low awareness. Improved early detection and monitoring in high-risk groups are needed.

Acute kidney injury (AKI) is a concerned complication in patients with cancer receiving anti-PD-1/PD-L1 therapy, with severe AKI linked to adverse outcomes. Here, we constructed and validated a predictive model for severe AKI in these patients. Patients administered anti-PD-1/PD-L1 antibody at the Dongyang People’s Hospital from January 2019 to December 2023 (831patients) were included and randomly assigned into training and testing sets in a 7:3 ratio. An external validation dataset (907 patients) was obtained from Zhejiang Provincial People’s Hospital. Severe AKI was defined AKI stages 2 and 3, based on the kidney disease improving global outcomes criteria. Severe AKI occurred in 4.2% (73/1738) of patients: 5.3% (31/581), 5.2% (13/250), and 3.2% (29/907) in the training, testing, and external validation sets, respectively. Overall survival was significantly lower in patients with severe AKI. In the training set, a nomogram for severe AKI was constructed using three predictive factors: higher systolic blood pressure, lower serum albumin level, and diuretic use. In the training set, the model achieved C-indices of 0.850, 0.829, and 0.808 for predicting severe AKI at 90, 180, and 360 days, respectively. Corresponding C-indices in the test set were 0.710, 0.775, and 0.857, while those in the external validation cohort reached 0.720, 0.772, and 0.757, demonstrating strong discriminability. Calibration charts and decision curve analyses confirmed its calibration capability and clinical utility. The developed nomogram aids in predicting severe AKI risk in patients receiving anti-PD-1/PD-L1 antibodies and supports effective preventive interventions.

OBJECTIVES:This study aims to investigate the changes of circulating natural killer (NK) cells and their TIGIT expression diversities, and further explore the impact of TIGIT expression on the activity and function of NK cells in rheumatoid arthritis (RA) patients. METHODS:We comparatively assessed and compared the changes of NK cells, as well as their TIGIT expressions, among 53 RA patients, 23 healthy controls and 11 osteoarthritis (OA) patients using flow cytometry and in vitro cultures. CD25 and CD69 expression levels were used to evaluate the activation of NK subsets, and CD107α and GZMB expressions levels, and IFN-γ production abilities were detected to indicate the function of NK subsets. RESULTS:Circulating CD56brightNK cell levels were significantly elevated, while NKT cell levels were notably reduced in RA patients. In addition, NK cells manifested more activated phenotypes and enhanced function in RA. Meanwhile, TIGIT expression on NK cells and subsets was significantly reduced, with an imbalanced TIGIT/CD226 ratio. TIGIT-expressing NK subsets showed lower CD25 expression levels and weakened IFN-γ production abilities in RA patients. Furthermore, in vitro blockade of TIGIT pathway with anti-TIGIT antibody enhanced NK cell activity and function, while activation of TIGIT pathway with TIGIT-Fc chimera protein down-regulated NK cells activity and function. CONCLUSION:Our results showed that decreased TIGIT expressions in RA patients and the TIGIT signalling pathway may participate in the activation and function of NK subsets, which show new insight for the exploration of RA pathogenesis.

BACKGROUND Immune checkpoint inhibitors (ICIs) are a new class of antitumor agents. They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells. ICIs also modulate regular immune cell activity, affecting the immune system and causing immune-related adverse events. The renal system is sometimes affected by these adverse events. Currently, the literature on ICIs-related glomerular injuries is scarce. CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis (GPA) 3 weeks after treatment with the anti-programmed cell death-1 inhibitor, tislelizumab. The patient experienced proteinuria, hematuria, and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cytoplasmic antibody (ANCA)-cytoplasmic type. Renal biopsy confirmed ANCA-associated vasculitis, and GPA was finally diagnosed. The patient received pulse treatment with glucocorticoids and cyclophosphamide, and renal function improved. After self-discontinuation of the drug, the disease recurred, and the original treatment regimen was continued. However, the patient’s renal function continued to deteriorate. CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab. However, follow-up and patient education are needed.

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients’ prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs).Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was evaluated.Results: Among the patients taking immunosuppressive medication, PI was observed in 548 (6.9%). The median time of PI occurrence after immunosuppressive therapy was 123.0 (interquartile range: 63.0, 436.0) days. Thirteen statistically significant independent predictors (sex, age, hypertension, DM, malignant tumour, use of biologics, use of CNIs, use of methylprednisolone at 500 mg, use of methylprednisolone at 40 mg, use of methylprednisolone at 40 mg total dose, use of oral glucocorticoids, albumin level, and haemoglobin level) were screened using the LASSO algorithm and multivariate COX regression analysis. The PIP model built on these features performed reasonably well, with the developing C-index of 0.87 (sensitivity: 85.4%; specificity: 81.0%) and validation C-indices of 0.837, 0.829, 0.832 and 0.830 for predicting 90-, 180-, 270- and 360-day PI probability, respectively. The decision curve analysis (DCA) and calibration curves displayed excellent clinical utility and calibration performance of the nomogram.Conclusion: The PIP model presented herein could aid in the prediction of PI risk in individual patients who receive immunosuppressive treatment and help personalise clinical decision-making.

ABSTRACT Background VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). Methods In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. Results The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1–2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change −2.0 mg/dL; 95% confidence interval −2.7, −1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change −1.6 (−2.2, −1.0), −1.8 (−2.4, −1.2) and −1.4 (−2.2, −0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. Conclusion VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number NCT04551300

PurposeTo develop and validate a web-based nomogram for predicting new incident chronic kidney disease (CKD) within 4 years in a cohort undergoing routine physical examination from two health examination centers.MethodsOne center was utilized for training and internal validation of a nomogram model involving 6515 patients, while a separate center was employed for external validation with 3152 patients. Sixteen candidate predictors, including patient demographics, medical histories, physical examination, and laboratory test data, were included in this study to ascertain factors linked to new incident CKD. A nomogram was created to predict CKD risks using a logistic model. The nomogram's performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis.ResultsOut of the 9667 healthy individuals included in the study with mean age of 46 years, sex ratio (male/female) of 1.69 (6075/3592), 118 (2.59%), 51 (2.61%), and 60 (1.90%) individuals developed CKD in the training (n = 4563), internal validation (n = 1952), and external validation (n = 3152) datasets, respectively. Age, history of diabetes mellitus, systolic blood pressure, serum creatinine, albumin, and triglyceride levels were used to build the nomogram, which yielded excellent discrimination ability (training cohort, AUC = 0.8806, 95% confidence interval [CI] 0.8472-0.9141; internal validation cohort, AUC = 0.8506, 95% CI 0.7856-0.9156; external validation cohort, AUC = 0.9183, 95% CI 0.8698-0.9669). We further developed a web-based calculator for convenient application (https://luochuxuan.shinyapps.io/dynnomapp/).ConclusionOur web-based nomogram accurately predicted CKD risks in Chinese health individuals and can be easily used in clinical settings.

Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4 weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). After 4, 12, and 24 weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5 g/L, 104 g/L, and 106.5 g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91 g/L, 94.5 g/L, and 94.5 g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels.

Purpose The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. Materials and methods This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. Results No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. Conclusions This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome.

Objective Antibiotic treatments are known to disturb gut microbiota, but their effects on the mucosal barrier and extraintestinal diseases are rarely discussed. The aim of this study was to evaluate and visualize the impact of antibiotics on colonic mucus and the microbial community, and to assess whether intestinal dysbacteriosis is involved in the pathogenesis and progression of extraintestinal diseases in vivo. Materials and Methods Twenty-one SD rats were randomly assigned into three groups followed by different experimental treatments. The albumin-creatinine ratio, urinary protein and occult blood semi-quantified test were tested. Fecal samples were collected at different time points (0,4, and 12 weeks) for 16S rRNA gene sequencing. Colon and kidney specimens were examined using light microscopy and transmission electron microscopy (TEM) to identify morphological changes. Results Ceftriaxone intervention for one week did not cause any symptoms of diarrhea or weight loss, but the alpha and beta diversities of gut microbiota decreased quickly and significantly, a lower Firmicutes/Bacteroidetes (F/B) ratio was observed. At week 12, although the alpha and beta diversities increased to a level similar to that of the control (CON) group, LEfSe analysis indicated that the microbial community composition still differed significantly in each group. In addition, KEGG metabolic prediction revealed different metabolic functions in each group. TEM examination of colon revealed that dramatic morphological changes were observed in the ceftriaxone (Cef) group, wherein microvilli were misaligned and shortened significantly and morphologically intact bacteria were seen on the epithelial cell surface. TEM examination of kidneys from the Cef group showed characteristic glomerular changes in the form of widely irregularly thickened glomerular basement membrane (GBM) and foot process fusion or effacement; mild thickening of the GBM and foot process fusion was detected when ceftriaxone and Resatorvid (TAK242, an inhibitor of TLR4 signaling) are used together in the ceftriaxone + TAK242 (TAK) group. Conclusions Short-term use of ceftriaxone induced dynamic changes of gut microbiota and lead to intestinal barrier disruption and ultrastructural changes of kidneys in the SD rats. Moreover, interference with the TLR4-dependent signaling pathway can alleviate the damage to the intestinal barrier and kidney.

Anti-PD-1/PD-L1 antibodies are widely used in anti-cancer therapy. While they have improved cancer prognoses, immune-related adverse events, which can cause acute kidney injury (AKI), cannot be ignored. The purpose of this retrospective cohort study was to assess the incidence, risk factors, and prognosis of AKI associated with anti-PD-1/PD-L1 antibodies. Patients who received anti-PD-1/PD-L1 antibody treatment at our hospital between January 2018 and December 2022 were enrolled. Clinical information, combined medications, concomitant diseases, tumor types, and laboratory indicators were collected from patient records, and the incidence of AKI was determined. The risk factors for AKI were assessed using univariate and multivariate logistic regression analyses. Overall, 1418 patients were enrolled. The median follow-up time was 112 days and 92 (6.5%) developed AKI. The median time from the initial anti-PD-1/PD-L1 antibody treatment to AKI was 99.85 days. Head and neck cancer and combined use of diuretics, non-steroidal anti-inflammatory drugs (NSAIDs), lower hemoglobin level, and other types of chemotherapeutic drugs were independent risk factors for AKI. The complete recovery, partial recovery, non-recovery, and unknown AKI rates were 7.6%, 28.3%, 52.2%, and 11.9%, respectively. Kidney biopsies were performed on two patients with AKI and pathology confirmed diagnosis of acute tubulointerstitial nephritis. In this cohort, AKI was not uncommon in patients treated with anti-PD-1/PD-L1 antibodies; therefore, it is necessary to monitor renal function and identify AKI early, especially in patients with head and neck tumors. Improving anemia and minimizing the use of diuretics, NSAIDs, and chemotherapeutics may reduce AKI.

AimThe aims of this study were to analyze the proteomic differences in renal tissues from patients with diabetes mellitus (DM) and diabetic kidney disease (DKD) and to select sensitive biomarkers for early identification of DKD progression.MethodsPressure cycling technology–pulse data-independent acquisition mass spectrometry was employed to investigate protein alterations in 36 formalin-fixed paraffin-embedded specimens. Then, bioinformatics analysis was performed to identify important signaling pathways and key molecules. Finally, the target proteins were validated in 60 blood and 30 urine samples.ResultsA total of 52 up- and 311 down-regulated differential proteins were identified as differing among the advanced DKD samples, early DKD samples, and DM controls (adjusted p<0.05). These differentially expressed proteins were mainly involved in ion transport, apoptosis regulation, and the inflammatory response. UniProt database analysis showed that these proteins were mostly enriched in signaling pathways related to metabolism, apoptosis, and inflammation. NBR1 was significantly up-regulated in both early and advanced DKD, with fold changes (FCs) of 175 and 184, respectively (both p<0.01). In addition, VPS37A and ATG4B were significantly down-regulated with DKD progression, with FCs of 0.140 and 0.088, respectively, in advanced DKD and 0.533 and 0.192, respectively, in early DKD compared with the DM control group (both p<0.01). Bioinformatics analysis showed that NBR1, VPS37A, and ATG4B are closely related to autophagy. We also found that serum levels of the three proteins and urine levels of NBR1 decreased with disease progression. Moreover, there was a significant difference in serum VPS37A and ATG4B levels between patients with early and advanced DKD (both p<0.05). The immunohistochemistry assaay exhibited that the three proteins were expressed in renal tubular cells, and NBR1 was also expressed in the cystic wall of renal glomeruli.ConclusionThe increase in NBR1 expression and the decrease in ATG4B and VPS37 expression in renal tissue are closely related to inhibition of the autophagy pathway, which may contribute to DKD development or progression. These three proteins may serve as sensitive serum biomarkers for early identification of DKD progression.

Background: Diabetic nephropathy (DN) is in the first place of the causes that lead to end-stage renal disease in the world. Thus, it is urgent to develop a novel diagnostic or therapeutic strategy that could stop the progression of diabetic nephropathy. Methods: RNA-sequencing was conducted in high glucose (HG)-treated MPC5 cells (podocytes). Cell morphology was examined under a light microscope. Upon high-glucose challenge, the effects of lncRNA Hoxb3os overexpression on MPC5 cells apoptosis, viability, autophagy and Akt-mTOR signaling were evaluated using flow cytometry, Cell Counting Kit-8, qRT-PCR, and Western blotting. TUNEL staining and ELISA were performed to confirm the establishment of DN model in db/db mice. Results: High-glucose exposure dramatically altered lncRNA expression profile in MPC5 cells (fold change>2), including 305 upregulated lncRNAs and 451 downregulated lncRNAs. LncRNA Hoxb3os expression was significantly reduced in the HG-induced podocyte damage model, as well as in the renal tissues from db/db mice with spontaneous DN. Overexpression of Hoxb3os significantly reduced the apoptosis rate and increased the viability of MPC5 cells under HG conditions. Further study revealed that exogenous Hoxb3os increased autophagy level in HG-exposed MPC5 cells via abrogating Akt-mTOR signaling pathway and that the process was possibly implicated in the upregulation of SIRT1. Conclusion: LncRNA Hoxb3os protected podocytes from HG-induced damage by regulating Akt-mTOR pathway and cell autophagy. Thus, lncRNA Hoxb3os appears as a potential biomarker in the diagnosis and treatment of DN in the future.

Background: Our aim was to evaluate the safety and efficacy of low-dose mineralocorticoid receptor antagonists (MRAs) in dialysis patients.Methods: We systematically searched PubMed, EMBASE, and Cochrane libraries for clinical trials on the use of MRAs in dialysis patients. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence.Results: We identified nine randomized controlled trials including 1128 chronic dialysis patients. In terms of safety, when hyperkalemia was defined as serum potassium level ≥5.5 mmol/L, low-dose MRAs were significantly associated with hyperkalemia (relative risk [RR] 1.76, 95% CI 1.07–2.89, P = 0.02); however, when hyperkalemia was defined as serum potassium level ≥6.0 mmol/L or serum potassium level ≥6.5 mmol/L, no significant association was observed between low-dose MRAs and hyperkalemia (RR 1.40, 95% CI 0.83–2.37, P = 0.20; RR 1.98, 95% CI 0.91–4.30, P = 0.09, respectively). Use of low-dose MRAs can reduce CV mortality by 57% compared with the control group (RR 0.43, 95% CI 0.25–0.75, P = 0.003). Similarly, the RR of all-cause mortality for the low-dose MRAs group was 0.44 (95% CI 0.28–0.68, P = 0.0003).Conclusion: Low-dose MRAs may benefit dialysis patients without significantly increasing moderate to severe hyperkalemia.