Efficacy and safety of rituximab for primary nephrotic syndrome with acute kidney injury: A two-center prospective cohort study.

The purpose of this study was to investigate the efficacy and safety of a low-dose Rituximab (RTX) regimen driven by peripheral blood B lymphocyte count in the treatment of adult patients with nephrotic syndrome (NS) complicated with acute kidney disease (AKI). We conducted a prospective single-arm study to evaluate the effect of B cells-driven RTX regimen. Patients with NS (MCD, FSGS, MN, IgAN) complicated with AKI fulfilling the inclusion criteria were eligible for this study. Patients were followed up at intervals of 2 months. Student's t-test and Chi-squared test were used to analyze normally distributed continuous variables and non-normally distributed continuous variables, respectively. From August 2018 to January 2022, 23 patients met the inclusion criteria and agreed to participate in the study. 3, 9, and 11 patients were AKI stage 1, 2, and 3, respectively. From baseline to the latest follow-up, 20 patients had complete and partial recovery of renal function. Accompanied by depletion of B cells, significant reduction of urinary protein excretion, serum total cholesterol, and the number of relapses were observed during the 12 months after the first RTX infusion as compared with during the 12 months before RTX injection. The number of patients who maintained steroids and immunosuppressive medications also remarkably decreased. This study indicates that the targets-driven treatment of low-dose RTX can achieve a high remission rate and alleviate the loss of kidney function in treating NS with AKI. The long-term efficacy, side effects, and therapeutic economics of RTX are reasonable.

Central versus ambulatory blood pressure for predicting mortality and cardiovascular events in hemodialysis patients: a multicenter cohort study.

OBJECTIVE: Studies in the general population suggest that central blood pressure (BP) may be superior to peripheral BP in risk assessment. Although ambulatory brachial BP is recognized as the most reliable BP measurement in the dialysis population, there is no comparison of office central BP with ambulatory BP regarding risk stratification in these patients. METHODS: In a multicenter prospective study of dialysis patients, central BP was measured noninvasively on a midweek nondialysis day, with interdialytic ambulatory BP and predialysis BP also collected. The primary outcomes were a composite of major adverse cardiovascular events (MACE) and all-cause mortality. Agreement between central and ambulatory BP was assessed using Cohen's Kappa index and Bland--Altman plot. Linear and nonlinear Cox regression models were used to determine the association of BP parameters with outcomes. RESULTS: A total of 368 patients were recruited and 366 underwent central BP measurement. Central BP had a moderate agreement with ambulatory BP in defining hypertension (κ = 0.42) with wide limits of agreement in Bland--Altman analysis. After a median follow-up of 51.5 months, central pulse pressure, ambulatory SBP and ambulatory pulse pressure were associated with all-cause mortality, whereas all BP parameters, except for predialysis DBP, were significant predictors of MACE. However, whenever evaluated in a stepwise variable selection Cox model, only ambulatory pulse pressure, but not any central BP, was determined as the best candidate for prediction of both all-cause mortality and MACE. Nonlinear Cox models revealed no significant nonlinear trend of the association between central BP and outcomes. CONCLUSION: Central BP is predictive of all-cause mortality and cardiovascular events in dialysis patients but its prognostic value does not outperform ambulatory peripheral BP. Our data support the superiority of ambulatory BP in the dialysis population.

C-X-C Motif Chemokine Ligand 16 Is a Potent Predictor of Outcomes in Dialysis Patients.

INTRODUCTION: C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. METHODS: This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. RESULTS: Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). CONCLUSION: Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target.

The unique molecular mechanism of diabetic nephropathy: a bioinformatics analysis of over 250 microarray datasets.

BACKGROUND/AIMS: Diabetic nephropathy (DN) is one of the main causes of end-stage kidney disease worldwide. Emerging studies have suggested that its pathogenesis is distinct from nondiabetic renal diseases in many aspects. However, it still lacks a comprehensive understanding of the unique molecular mechanism of DN. METHODS: A total of 255 Affymetrix U133 microarray datasets (Affymetrix, Santa Calra, CA, USA) of human glomerular and tubulointerstitial tissues were collected. The 22 215 Affymetrix identifiers shared by the Human Genome U133 Plus 2.0 and U133A Array were extracted to facilitate dataset pooling. Next, a linear model was constructed and the empirical Bayes method was used to select the differentially expressed genes (DEGs) of each kidney disease. Based on these DEG sets, the unique DEGs of DN were identified and further analyzed using gene ontology and pathway enrichment analysis. Finally, the protein-protein interaction networks (PINs) were constructed and hub genes were selected to further refine the results. RESULTS: A total of 129 and 1251 unique DEGs were identified in the diabetic glomerulus (upregulated n = 83 and downregulated n = 203) and the diabetic tubulointerstitium (upregulated n = 399 and downregulated n = 874), respectively. Enrichment analysis revealed that the DEGs in the diabetic glomerulus were significantly associated with the extracellular matrix, cell growth, regulation of blood coagulation, cholesterol homeostasis, intrinsic apoptotic signaling pathway and renal filtration cell differentiation. In the diabetic tubulointerstitium, the significantly enriched biological processes and pathways included metabolism, the advanced glycation end products-receptor for advanced glycation end products signaling pathway in diabetic complications, the epidermal growth factor receptor (EGFR) signaling pathway, the FoxO signaling pathway, autophagy and ferroptosis. By constructing PINs, several nodes, such as AGR2, CSNK2A1, EGFR and HSPD1, were identified as hub genes, which might play key roles in regulating the development of DN. CONCLUSIONS: Our study not only reveals the unique molecular mechanism of DN but also provides a valuable resource for biomarker and therapeutic target discovery. Some of our findings are promising and should be explored in future work.

Efficacy and Safety of Chinese Herbal Formula Granules in Treating Chronic Kidney Disease Stage 3: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: It is generally considered that traditional Chinese medicine (TCM) therapy postpones the progression of some chronic kidney diseases (CKDs). Chinese medicine herbs are widely applied in TCM therapy. We aimed to evaluate clinical efficacy and safety of Chinese herbal formula granules in patients with CKD stage 3 through a prospective randomized controlled study. METHODS: A total of 343 participants with CKD stage 3 were recruited from 9 hospitals in Jiangsu Province between April 2014 and October 2016. Participants were randomly assigned to a treatment or control group. Patients in the treatment group orally took Chinese herbal formula granules twice a day, while controls received placebo granules. The duration of intervention was 24 weeks. Primary outcomes were 24-hour proteinuria, serum creatinine, and eGFR, which were measured every 4 weeks. RESULTS: There was no statistical difference in 24-hour proteinuria between the two groups (0.97 ± 1.14 g/d vs. 0.97 ± 1.25 g/d). Patients in the treatment group had significantly lower serum creatinine level (130.78 ± 32.55 µmol/L versus 149.12 ± 41.27 µmol/L) and significantly higher eGFR level (55.74 ± 50.82 ml/min/1.73·m2 versus 44.46 ± 12.60 ml/min/1.73·m2) than those in the control group (P < 0.05). There was no significant difference between two groups in the incidence of adverse events. CONCLUSION: The treatment adopting Chinese herbal formula granules for 24 weeks improved kidney function of patients with CKD stage 3.

Evaluation of anemia, malnutrition, mineral, and bone disorder for maintenance hemodialysis patients based on bioelectrical impedance vector analysis (BIVA).

BACKGROUND: ESRD (End-stage renal disease) treatment is a comprehensive medical process and requires numerous serological biochemical tests (SBTs) in diagnosis. To reduce these invasive, expensive, cumbersome, and time-consuming SBTs, there is a need to develop an alternative serological biochemical composition evaluation method. Bioelectrical impedance analysis (BIA) is affected by body's chemical and physical components, which might be correlated with serological biochemical composition and can be potentially used to evaluate biochemical composition in hemodialysis patient treatments. In this work, the relationship of classic and specific bioelectrical impedance vector analysis (BIVA) with major serological biochemical indexes in maintenance hemodialysis (MHD) patients was examined. METHODS: Bioelectrical and biochemical datasets were measured from 280 women and 408 men and formed 3872 effective biochemical-bioelectrical records in total. Statistical analysis was performed. RESULTS: The results show that BIVA vectors have strong relationship with phosphorus, hemoglobin, and PTH in both male and female groups. Strong correlation was also observed between Ca, albumin, CHOL, LDLC, and BIVA vectors in the male group. In the female group, a significant correlation was observed between classic BIVA values and NT-proBNP. SVM models are effective for classifying biochemical indexes. CONCLUSIONS: The obtained correlations and SVM classification models imply that BIVA can be used as a preliminary tool to evaluate and classify the degree of anemia, malnutrition, fluid overload, and mineral and bone disorder (MBD) in MHD patients by reducing the number of SBTs.

3D Graphene Materials: From Understanding to Design and Synthesis Control.

Carbon materials, with their diverse allotropes, have played significant roles in our daily life and the development of material science. Following 0D C60 and 1D carbon nanotube, 2D graphene materials, with their distinctively fascinating properties, have been receiving tremendous attention since 2004. To fulfill the efficient utilization of 2D graphene sheets in applications such as energy storage and conversion, electrochemical catalysis, and environmental remediation, 3D structures constructed by graphene sheets have been attempted over the past decade, giving birth to a new generation of graphene materials called 3D graphene materials. This review starts with the definition, classifications, brief history, and basic synthesis chemistries of 3D graphene materials. Then a critical discussion on the design considerations of 3D graphene materials for diverse applications is provided. Subsequently, after emphasizing the importance of normalized property characterization for the 3D structures, approaches for 3D graphene material synthesis from three major types of carbon sources (GO, hydrocarbons and inorganic carbon compounds) based on GO chemistry, hydrocarbon chemistry, and new alkali-metal chemistry, respectively, are comprehensively reviewed with a focus on their synthesis mechanisms, controllable aspects, and scalability. At last, current challenges and future perspectives for the development of 3D graphene materials are addressed.

Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy.

BACKGROUND: M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. METHODS: A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. RESULTS: The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P < 0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P = 0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P = 0.015) and serum albumin (23.28 vs. 27.95 g/L, P = 0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P = 0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. CONCLUSION: Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

Ultrafast, Low-Cost, and Mass Production of High-Quality Graphene.

Fast, mass, and low-cost production of high-quality graphene, which is alluring, remains a great challenge, even though some approaches have shown potential for mass synthesis of graphene. Very recently a great breakthrough was made by Tour and co-workers (Nature 2020, 577, 647-651): in just a second, easily exfoliated and highly crystalline graphene was produced from abundant carbon-containing species by cost-effective flash Joule heating with a low energy input of 7.2 kJ per gram graphene. Such an ultrafast, economic, and scalable process for high-quality graphene production can be considered as a milestone in the graphene field and is highlighted in this article.

Decorating g-C3N4 with alkalinized Ti3C2 MXene for promoted photocatalytic CO2 reduction performance.

Photocatalytic reduction of carbon dioxide (CO2) under visible light irradiation for producing high-value fuel has attracted tremendous attention in recent years. In this study, titanium carbide MXene (Ti3C2) was used as a noble metal-free co-catalyst by simply mixing graphitic carbon nitride (g-C3N4) and alkalized Ti3C2. The carbon monoxide evolution rate of the optimized composite (5%TCOH-CN) from photocatalytic reduction of CO2 was 5.9 times higher than that of pure g-C3N4. Alkalized Ti3C2 was responsible for the superior photocatalytic activity due to its excellent electrical conductivity and large CO2 adsorption capacity. Furthermore, the separation of the photo-induced electron-hole pairs was greatly enhanced because of the large Fermi level difference between alkalized Ti3C2 and pure g-C3N4. This work demonstrates the potential of MXenes as noble metal-free co-catalyst for photocatalysis processes such as carbon dioxide reduction reaction and nitrogen reduction reaction.

A direct Z-scheme Bi2WO6/NH2-UiO-66 nanocomposite as an efficient visible-light-driven photocatalyst for NO removal.

To explore an efficient photocatalyst for NO pollution, a direct Z-scheme photocatalytic system is successfully fabricated by coupling Bi2WO6 with NH2-UiO-66 via a simple hydrothermal synthesis technique. The Z-scheme system promotes the NO photocatalytic oxidation activity with an optimum NO removal rate of 79%, which is 2.7 and 1.2 times that obtained by using only pristine Bi2WO6 and NH2-UiO-66, respectively. Simultaneously, superior selectivity for converting NO to NO3 -/NO2 - is observed. The enhanced photocatalytic performance of the Bi2WO6/NH2-UiO-66 hybrids is attributed to the following two aspects: (i) large specific area of NH2-UiO-66, which exposes more active sites and is beneficial to the adsorption and activation of NO; (ii) outstanding Z-scheme structure constructed between BiWO6 and NH2-UiO-66, which can improve the efficiency of the separation of electron-hole pairs and preserves the strong oxidation ability of hybrids. ESR analysis shows that ·O2 - and ·OH contribute to NO removal. A possible photocatalytic mechanism of NO oxidation on the direct Z-scheme photocatalyst (BWO/2NU) under visible light irradiation is proposed. This work displays the BWO/2NU hybrid's potential for treating low-concentration air pollutants, and the proposed Z-scheme photocatalyst design and promotion mechanism may inspire more rational synthesis of highly efficient photocatalysts for NO removal.

A comparison of clinical features between idiopathic membranous nephropathy patients with and without serum antibody against phospholipase A2 receptor.

Patients with idiopathic membranous nephropathy (IMN) can be categorized into phospholipase A2 receptor (PLA2R)-associated and non-PLA2R-associated cases, according to serum PLA2R antibody status. The present study aimed to determine whether clinical features differed between these.A total of 89 patients with IMN were retrospectively recruited for the present study. Serum PLA2R-Ab levels were determined by time-resolved fluoroimmunoassay. Furthermore, the relationship between serum PLA2R antibody levels and their responses to immunosuppressants among patients with a complete follow-up period, which was defined as at least 1 year, was analyzed.Among these enrollees, 71 (80.0%) patients were positive for serum PLA2R antibody. Furthermore, patients with PLA2R-associated IMN had significantly higher age (with vs without, 54.31 ±â€Š14.03 vs 46.67 ±â€Š13.30 years old; P = .04), proteinuria (4.32 ±â€Š1.84 vs 3.29 ±â€Š1.90 g/d, P = .039), and serum albumin (25.33 ±â€Š9.60 vs 31.38 ±â€Š9.52 g/L, P = .019), but had lower serum immunoglobulin G (6.83 ±â€Š2.89 vs 8.72 ±â€Š2.95 g/L, P = .016) and erythrocyte sedimentation rate (47.31 ±â€Š32.11 vs 26.33 ±â€Š27.94, P = .013), when compared to IMN patients without PLA2R. Furthermore, IMN patients without PLA2R exhibited a better response to immunosuppressants, when compared to patients with PLA2R-associated IMN (without vs with, 66.7% vs 62.5% at 6 months and 100% vs 87.5% at 12 months), but the difference was not statistically significant.Patients with PLA2R-associated IMN had higher disease severity than IMN patients without PLA2R. Furthermore, PLA2R negative patients had a better response to immunosuppressive therapies than PLA2R-positive patients, but the difference was not statistically significant.

Basic Research in Diabetic Nephropathy Health Care: A study of the Renoprotective Mechanism of Metformin.

The anti-aging gene klotho is closely related to kidney disease, and an increase in the level of the klotho protein inhibits the progression of various kidney diseases. According to clinical studies, dimethyl-biguanide hydrochloride (DMBG) reduces the urinary protein level in patients with diabetic nephropathy to protect the kidney, but the specific renoprotective mechanism remains unclear. In this study, the application of DMBG partially alleviates the pathological changes in the kidneys of db/db mice, increases the level of the klotho protein in the blood, urine and kidney tissues of the mice, and reduces the levels of the mTOR and p-mTOR proteins. The effects of high glucose and DMBG on klotho and the mTOR pathway in MDCK cells were analyzed at the cellular level. High glucose stimulation activates mTOR pathway and decreases the activity of MDCK cells. DMBG decreases the level of the mTOR protein and reverses the effect of hyperglycaemic stimulation on the activity of MDCK cells. After inhibiting the expression of the klotho protein, DMBG is unable to decrease the level of the mTOR protein. Therefore, klotho plays an important role in the mechanism by which DMBG inhibits the mTOR pathway to protect renal function.

Reed-derived fluorescent carbon dots as highly selective probes for detecting Fe3+ and excellent cell-imaging agents.

A kind of highly selective and sensitive fluorescent probe for detecting Fe3+, carbon dots (CDs), was prepared with renewable reed naturally containing C, N, O, and S elements as a green and eco-friendly carbon source by a simple hydrothermal process. The fluorescence of CDs without purification and surface modification can be quenched by Fe3+ in a wide concentration range of 0 to 362 µmol L-1 (concentration of Fe3+), with detection limits as low as 0.014 µmol L-1 in 0-50 µmol L-1. Characterizations, such as TEM, XPS, Raman and FTIR, confirmed that the static quenching mechanism involved the generation of non-luminescent complexes between Fe3+ and functional groups (carboxyl group, sulfur-oxyl group and hydroxyl group) on the surface of CDs and with the aggregation of CDs. More importantly, CDs had good biocompatibility and nontoxicity according to an MTT cell-viability assay, and cells labeled with CDs emitted blue, green and red color fluorescence. Thus, the static quenching mechanism was confirmed. So, this reed-derived natural CD solution can be utilized in detecting Fe3+, culture cells, and cell imaging.

Leflunomide versus cyclophosphamide in the induction treatment of proliferative lupus nephritis in Chinese patients: a randomized trial.

OBJECTIVES: A prospective, multi-center, randomized controlled study was conducted to evaluate the efficacy and safety of a 24-week course low-dose leflunomide combined with prednisone in the induction treatment of proliferative lupus nephritis in Chinese patients. METHOD: Patients (n = 100) with biopsy-proved proliferative lupus nephritis were enrolled in this study. They were randomized into two groups and received either leflunomide or cyclophosphamide in conjunction with prednisone for 24 weeks. Leflunomide was given orally with a loading dose of 40 mg/day for 3 days followed by 20 mg/day. Intravenous cyclophosphamide was administered monthly at a dosage of 0.8-1.0 g. The primary efficacy outcome was the frequency of complete remission and partial remission at week 24. The secondary outcomes included changes of urinary protein excretion, serum albumin, complement 3, anti-dsDNA antibody level, and systemic lupus erythematosus disease activity index (SLEDAI) after 24-week therapy. RESULTS: Of 100 patients, 48 received leflunomide combined with prednisone and other 52 received cyclophosphamide with concomitant prednisone. There were no statistically significant differences between groups in complete remission rate and partial remission rate. At week 24, 23% of patients in the leflunomide group and 27% of patients in the cyclophosphamide group achieved complete remission (P = 0.64), while 56% of patients in the leflunomide group and 42% of patients in the cyclophosphamide group achieved partial remission at week 24 (P = 0.16). SLEDAI, serum albumin, complement 3, anti-dsDNA antibody level, and urinary protein excretion improved significantly in both groups. No significant difference was seen in the changes of clinical parameters after therapy between the two groups. There was no significant difference in side effects in both groups. CONCLUSIONS: Compared with cyclophosphamide, low-dose leflunomide in combination with prednisone showed both effectiveness and safety in the induction therapy of proliferative lupus nephritis in Chinese patients.

Association of betaine with blood pressure in dialysis patients.

Mechanisms underlying elevated blood pressure in dialysis patients are complex as a variety of non-traditional factors are involved. We sought to explore the association of circulating betaine, a compound widely distributed in food, with blood pressure in dialysis patients. We used baseline data of an ongoing cohort study involving patients on hemodialysis. Plasma betaine was measured by high performance liquid chromatography in 327 subjects. Blood pressure level was determined by intradialytic ambulatory blood pressure monitoring. The mean age of the patients was 52.6 ± 11.9 years, and 58.4% were male. Average interdialytic ambulatory systolic and diastolic blood pressure were 138.4 ± 22.7 mm Hg and 84.4 ± 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 µmol/L. Multiple linear regression analysis revealed significant associations of betaine with both systolic blood pressure (ß = -3.66, P = .003) and diastolic blood pressure (ß = -2.00, P = .004). The associations persisted even after extensive adjustment for cardiovascular covariates. Subgroup analysis revealed that the association between betaine and blood pressure was mainly limited to female patients. Our data suggest that alteration of circulating betaine possibly contributes to blood pressure regulation in these patients.

Ultrasensitive Quantitation of Anti-Phospholipase A2 Receptor Antibody as A Diagnostic and Prognostic Indicator of Idiopathic Membranous Nephropathy.

Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is useful for affirming the diagnosis of idiopathic membranous nephropathy (IMN). Time-resolved fluoroimmunoassay (TRFIA) is highly sensitive and quantitative for measuring serum PLA2R-Ab immunoglobulin (IgG). We measured PLA2R-Ab levels with TRFIA in sera from 172 patients with IMN (n = 69), secondary MN (n = 9), and those with other glomerulonephritis (n = 94) at the time of renal biopsy compared to healthy controls (n = 286). Serum anti-PLA2R-IgG levels in healthy volunteers ranged from 0.09-0.91 mg/L. We set the cutoff value of the anti-PLA2R-IgG titer at 0.91 mg/L, with a sensitivity of 84.06% for diagnosing IMN. Increasing the cut-off value to 2.025 mg/L altered the sensitivity for diagnosing IMN to 71.01%, but with 100% specificity. IMN patients had significantly higher serum anti-PLA2R-IgG levels compared to those with secondary MN. PLA2R-Ab titers negatively correlated with estimated glomerular filtration rate (eGFR). Patinets with high titers had significantly lower serum albumin and eGFR, higher proteinuria and serum creatinine levels, accompanied by a lower complete remission rate. High titers of PLA2R-Ab were associated with poor prognosis of patients with IMN. TRFIA-based quantification of anti-PLA2R-IgG can be a reliable approach for the diagnosis and prognostication of patients with IMN.

Response to immunosuppressive therapy in PLA2R- associated and non-PLA2R- associated idiopathic membranous nephropathy: a retrospective, multicenter cohort study.

BACKGROUND: According to renal M type phospholipase A2 receptor (PLA2R) immunohistochemistry, idiopathic membranous nephropathy (IMN) could be categorized into PLA2R-associated and non-PLA2R-associated IMN. We conducted a retrospective, multicenter cohort study with 91 patients to compare the effect of immunosuppressive therapy between PLA2R-associated and non-PLA2R-associated IMN patients. METHODS: A total of 91 biopsy-proven IMN patients from Huashan hospital and People's Hospital of Wuxi in past 5 years were collected into this study. IMN with positive PLA2R immunohistochemistry in kidney biopsies were designated as PLA2R-associated IMN. Seventy-eight of the 91 IMN patients was PLA2R-associated IMN and 13 were non-PLA2R-associated IMN. Forty-five patients were treated with prednisone plus cyclophosphamide (CTX), and 46 with prednisone plus calcineurin inhibitors (CNIs). The follow-up duration was 15 months. RESULTS: The total remission rate (76.9% versus 44.9%, p = 0.032) and complete remission rate (30.8% versus 2.6%, p = 0.003) were both significantly higher in the non-PLA2R-associated group than in the PLA2R-associated group at the 3rd month visit point, and at the 6th month time point, the complete remission rate was still significantly higher in the non-PLA2R-associated group (46.2% versus 11.5%,p = 0.007). But similar remission rates were found after the 9th month. Relapses were observed in 8 patients in PLA2R-associated group and none in non-PLA2R-associated group, although there was no significant difference between these two groups. CONCLUSION: Compared with the PLA2R-associated IMN, the non-PLA2R-associated IMN responded quicker to the immunosuppressive therapy.

Interaction of Soluble CXC Ligand 16 and Cardiac Injury Markers in Hemodialysis Patients.

BACKGROUND: Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients. METHODS: Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls. RESULTS: The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs. CONTROLS: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; p < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all p < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins. CONCLUSION: We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients.