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1.
Int Immunopharmacol ; 138: 112607, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38981222

ABSTRACT

OBJECTIVE: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA). METHODS: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival. RESULTS: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) µmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 µmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group. CONCLUSIONS: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic , Autoantibodies , Humans , Female , Male , Middle Aged , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , Aged , Retrospective Studies , Autoantibodies/blood , Autoantibodies/immunology , Glomerulonephritis/immunology , Glomerulonephritis/mortality , Glomerulonephritis/therapy , Glomerulonephritis/diagnosis , Glomerulonephritis/blood , Follow-Up Studies , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood
2.
Front Pharmacol ; 15: 1308309, 2024.
Article in English | MEDLINE | ID: mdl-38681199

ABSTRACT

Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.

3.
J Cancer ; 15(8): 2214-2228, 2024.
Article in English | MEDLINE | ID: mdl-38495490

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

4.
Front Biosci (Landmark Ed) ; 29(1): 45, 2024 01 23.
Article in English | MEDLINE | ID: mdl-38287825

ABSTRACT

Pancreatic cancer is a malignancy that affects the digestive tract and has a low 5-year survival rate of lower than 15%. Owing to its genetic mutation and metabolic complexity, pancreatic cancer is difficult to treat with surgical resection, radiotherapy, and chemotherapy. The predominant modality of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), primarily attributed to mutations in KRAS gene. Ferroptosis, an iron-mediated reactive oxygen species (ROS)-elevated nonapoptotic cell death caused by lipid peroxidation, is distinct from any other known type of cell death. Ferroptosis is closely related to the occurrence and progression of different types of cancers, including PDAC. Previous research has demonstrated that ferroptosis not only triggers cell death in PDAC and hampers tumor growth but also enhances the effectiveness of antitumor medications. In our review, we mainly focus on the core mechanism of ferroptosis, reveal its interrelationship with PDAC, and illustrate the progress of ferroptosis in different treatment methods of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Ferroptosis , Pancreatic Neoplasms , Humans , Ferroptosis/genetics , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Mutation , Cell Death
5.
J Cancer Res Clin Oncol ; 149(8): 5061-5070, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36326913

ABSTRACT

PURPOSE: Immune checkpoint inhibitor (ICI) therapy is now the stand of care for lung cancer. Due to the low incidence, the study of acute kidney injury (AKI) in lung cancer patients treated with ICIs was hardly reported. We focused on the incidence, characteristics, risk factors, and mortality of AKI in advanced lung cancer patients receiving PD-1 inhibitors. METHODS: We reviewed advanced lung cancer patients receiving PD-1 inhibitors between January 2018 to August 2020 at Jiangsu Province Hospital. Patients were followed up for 6 months. We used the logistic regression model to evaluate risk factors for AKI, and Kaplan-Meier method to assess the association between AKI and mortality. RESULTS: A total of 305 advanced lung cancer patients treated with PD-1 inhibitors. The median age was 64 years and 80.6% of patients were male. The incidence of AKI was 10.2%, and the incidence of ICI-AKI was 4.6%. Multivariate analysis showed that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR 2.509; 95% CI 1.053-5.974) and renin-angiotensin-aldosterone system (RAAS) inhibitors (OR 2.656; 95% CI 1.091-6.466) were risk factors for AKI. In addition, concomitant use of NSAIDs (OR 5.170; 95% CI 1.087-24.595) and RAAS inhibitors (OR 5.921; 95% CI 1.871-18.737), and the occurrence of extra-renal immune-related adverse events (OR 4.726; 95% CI 1.462-15.280) were significantly associated with ICI-AKI. ICI-AKI was not associated with mortality while severe AKI was associated with higher risk of mortality. CONCLUSION: AKI is common in advanced lung cancer patients treated with PD-1 inhibitors. The characteristics and risk factors of ICI-AKI were similar to those previously reported in other solid organ malignancies treated with ICIs. Severe AKI may indicate higher mortality.


Subject(s)
Acute Kidney Injury , Lung Neoplasms , Humans , Male , Middle Aged , Female , Immune Checkpoint Inhibitors/adverse effects , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Risk Factors , Anti-Inflammatory Agents, Non-Steroidal , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Retrospective Studies , Observational Studies as Topic
6.
Ren Fail ; 44(1): 2037-2045, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36408940

ABSTRACT

OBJECTIVE: To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival. METHODS: A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed. RESULTS: Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) µmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22-9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65-10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01-8.14, p = 0.047) were predictive of patient survival. CONCLUSIONS: Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.


Subject(s)
Anti-Glomerular Basement Membrane Disease , Glomerulonephritis , Humans , Male , Female , Middle Aged , Anti-Glomerular Basement Membrane Disease/diagnosis , Anti-Glomerular Basement Membrane Disease/therapy , Anti-Glomerular Basement Membrane Disease/pathology , Retrospective Studies , Glomerulonephritis/therapy , Glomerulonephritis/complications , Glomerular Basement Membrane/pathology , Kidney/pathology
7.
Front Immunol ; 13: 977377, 2022.
Article in English | MEDLINE | ID: mdl-36172377

ABSTRACT

Lupus Nephritis (LN) is the most common manifestation of severe organ damage for systemic lupus erythematosus (SLE) patients. Severe active LN could result in acute kidney injury (AKI), which could even require Kidney Replacement Therapy (KRT). Therefore, there needs to be a more proactive and safe induction therapy to quickly and effectively control renal immune inflammation, maintain kidney function or reverse kidney damage. While multiple clinical studies have proven the efficacy and safety of Belimumab in treating SLE and LN, these studies have not included cases of severe LN requiring KRT. We observed the effectiveness and safety of Belimumab in treating four severe active LN patients undergoing KRT. With Belimumab administered at a dosage of 10mg/kg, all four patients were able to discontinue KRT with no adverse events (AEs) to date ultimately. These cases provided an excellent basis for the application of Belimumab combined with standard therapy to LN patients with a medium to severe kidney injury.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/chemically induced , Lupus Nephritis/drug therapy
8.
Sci Total Environ ; 837: 155687, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35525362

ABSTRACT

Identifying the underlying ecological drivers of macroinvertebrate community assembly is fundamental to metacommunity ecology. Comparably, determining the influence of different drivers on beta diversity patterns can provide insight into processes governing community organization. Exploring the ecological drivers of metacommunity and beta diversity are major avenues to improve bioassessment, restoration, and river management, which are still poorly explored in China, especially in subtropical highly developed river networks. To address this gap, we use a dataset (macroinvertebrate communities and environmental variables) collected from the Yangtze River Delta, China to test the above ideas. We used the K-means clustering method to divide 405 river sites into three anthropogenic impacted groups, nearly pristine sites, moderately impacted sites, and heavily impacted sites, and subsequently used partial Mantel tests to investigate how species sorting and dispersal shaped the metacommunity that varied with the levels of anthropogenic impacts and to explore the responses of different components of beta diversity to environmental and spatial distances among sites for each group. Our results revealed that both species sorting and dispersal shape communities, but the importance of species sorting and dispersal varied with the levels of anthropogenic impacts. Nearly pristine sites were mostly shaped only by species sorting, while heavily impacted sites were shaped by dispersal. We also found that turnover was by far the dominant component of beta diversity across all levels of impact. Therefore, we encourage that environmental variables and spatial processes should be considered in bioassessment approaches. In addition, it is essential to focus on maintaining habitat heterogeneity and identifying and protecting regional species pools that could improve local biodiversity through dispersal for ecosystem management of the Yangtze River Delta of China.


Subject(s)
Ecosystem , Rivers , Biodiversity , China
9.
Future Oncol ; 18(16): 1951-1962, 2022 May.
Article in English | MEDLINE | ID: mdl-35232231

ABSTRACT

Aim: To explore the incidence, risk factors and overall outcome of the first episode of immune checkpoint inhibitor-related acute kidney injury (ICI-AKI) in Chinese patients receiving PD-1 inhibitors. Methods: Data for patients receiving PD-1 inhibitors at Jiangsu Province Hospital between December 2017 and January 2020 were retrospectively reviewed. Results: A total of 5.6% of 551 patients receiving PD-1 inhibitors developed ICI-AKI. Concomitant use of NSAIDs, ICI cycles and extrarenal immune-related adverse events may be independently associated with ICI-AKI. ICI-AKI may not be a risk factor for increased mortality or worse progression-free survival. Conclusions: ICI-AKI is relatively rare and its occurrence may not affect the overall 6-month outcome of patients receiving PD-1 inhibitors. Further studies are needed to verify these findings.


Immune checkpoint inhibitors (ICIs) have been more and more commonly used in patients with cancer. Therefore, it is important to understand the immune-related adverse events (irAEs), including immune-related renal adverse events, caused by ICIs. In this article, the authors explore the incidence, clinical features, risk factors and overall outcome of immune checkpoint inhibitor related-acute kidney injury (ICI-AKI) in Chinese patients treated with PD-1 inhibitors for the first time. Among 551 patients treated with PD-1 inhibitors, 65 patients experienced AKI and 31 patients experienced ICI-AKI. Patients with ICI-AKI may be more likely to receive nonsteroidal anti-inflammatory drugs, to receive PD-1 inhibitors for longer cycles or to experience extrarenal immune-related adverse events prior to or concomitant with ICI-AKI. The occurrence of ICI-AKI may not affect the survival time or disease progression of patients with cancer.


Subject(s)
Acute Kidney Injury , Immune Checkpoint Inhibitors , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , China/epidemiology , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Incidence , Male , Retrospective Studies
10.
ACS Nano ; 16(4): 6676-6686, 2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35293217

ABSTRACT

Currently, graphene films are expected to achieve real applications in various fields. However, the conventional synthesis methods still have intrinsic limitations, especially not being applicable on a surface with high curvature. Herein, an ultrafast synthesis method was developed for graphene and turbostratic graphite growth by a single subsecond pulse of microwaves generated by a household magnetron. We succeeded in growing high-quality around 10-layered turbostratic graphite in 0.16 s directly on the surface of an atomic force microscope probe and maintaining a tip curvature radius of less than 30 nm. The thus-produced probes showed high conductivity and tip durability. Moreover, turbostratic graphite film was also demonstrated to grow on the surface of dielectric Si flat substrates in a full coverage. Graphene can also grow on metallic Ni tips by this method. Our microwave ultrafast method can be used to grow high-quality graphene in a facile, efficient, and economical way.

11.
J Mol Cell Biol ; 14(2)2022 06 17.
Article in English | MEDLINE | ID: mdl-35142858

ABSTRACT

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers, and mummified legs. Because of the worsening symptoms and signs refractory to conventional therapies, treatment with human amnion-derived mesenchymal stem cells (hAMSCs) was approved. Preclinical release inspections of hAMSCs, efficacy, and safety assessment, including cytokine secretory ability, immunocompetence, tumorigenicity, and genetics analysis in vitro, were introduced. We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats, abnormal immune response tests in C57BL/6 mice, and tumorigenicity tests in neonatal Balbc-nu nude mice. After the preclinical research, the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers. When followed up to 15 months, the blood-based markers of bone and mineral metabolism improved, with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis, and 20 months later, the re-epithelialization restored the integrity of the damaged site. No infusion or local treatment-related adverse events occurred. Thus, this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multidifferentiation, re-epithelialization, and restoration of integrity.


Subject(s)
Calciphylaxis , Mesenchymal Stem Cells , Amnion , Animals , Calciphylaxis/complications , Calciphylaxis/therapy , Humans , Leukocytes, Mononuclear , Mice , Mice, Inbred C57BL , Mice, Nude , Rats , Ulcer/metabolism
12.
J Ren Nutr ; 32(2): 152-160, 2022 03.
Article in English | MEDLINE | ID: mdl-33727001

ABSTRACT

OBJECTIVES: The aim of this study is to analyze the association between the ratio of overhydration and extracellular water (OH/ECW) and the ratio of extracellular water and body cell mass (ECW/BCM) measured by bioelectrical impedance and outcomes of patients with acute kidney injury (AKI) requiring kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed using a body composition monitor before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors mainly included OH/ECW and ECW/BCM. The association between all-cause mortality and predictors were analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study with a median follow-up of 39 (interquartile range 8-742) days. The 28-day mortality, 90-day mortality, and 1-year mortality were 46.7%, 54.6%, and 60.5%, respectively. A high ratio of OH/ECW (adjusted hazard ratio per standard deviation, 1.45; 95% confidence interval = 1.15-1.82, P = .002) and a high ratio of ECW/BCM (adjusted hazard ratio per standard deviation, 1.33, 95% confidence interval = 1.07-1.64, P = .009) before KRT were associated with all-cause mortality during follow-up. Higher ECW/BCM rather than OH/ECW at 7th day was associated with poorer outcomes. Furthermore, a reduction of OH/ECW with an increase of ECW/BCM had higher 1-year mortality as compared to others (85.7% vs. 51.2%, P = .004) in patients who survived 7 days after KRT initiation. CONCLUSIONS: ECW/BCM performed better than OH/ECW in assessment of fluid status in AKI patients requiring KRT. This study suggested that a simple reduction of OH/ECW without decreasing ECW/BCM may not improve outcomes.


Subject(s)
Acute Kidney Injury , Heart Failure , Water-Electrolyte Imbalance , Acute Kidney Injury/complications , Acute Kidney Injury/therapy , Body Composition , Body Water , Cohort Studies , Electric Impedance , Female , Humans , Male , Renal Replacement Therapy , Water
13.
Blood Purif ; 51(3): 260-269, 2022.
Article in English | MEDLINE | ID: mdl-34161949

ABSTRACT

OBJECTIVE: The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. METHODS: We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. RESULTS: Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. CONCLUSIONS: Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.


Subject(s)
Coronary Artery Disease , Peritoneal Dialysis , Vascular Calcification , Humans , Middle Aged , Peritoneal Dialysis/adverse effects , Prospective Studies , Renal Dialysis/adverse effects
14.
Molecules ; 26(16)2021 Aug 15.
Article in English | MEDLINE | ID: mdl-34443528

ABSTRACT

Graphene has many excellent optical, electrical and mechanical properties due to its unique two-dimensional structure. High-efficiency preparation of large area graphene film is the key to achieve its industrial applications. In this paper, an ultrafast quenching method was firstly carried out to flow a single pulse current through the surface of a Si wafer with a size of 10 mm × 10 mm for growing fully covered graphene film. The wafer surface was firstly coated with a 5-nm-thick carbon layer and then a 25-nm-thick nickel layer by magnetron sputtering. The optimum quenching conditions are a pulse current of 10 A and a pulse width of 2 s. The thus-prepared few-layered graphene film was proved to cover the substrate fully, showing a high conductivity. Our method is simple and highly efficient and does not need any high-power equipment. It is not limited by the size of the heating facility due to its self-heating feature, providing the potential to scale up the size of the substrates easily. Furthermore, this method can be applied to a variety of dielectric substrates, such as glass and quartz.

15.
Front Oncol ; 11: 662731, 2021.
Article in English | MEDLINE | ID: mdl-34221977

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy. METHODS: We carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types. RESULTS: Ninety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3-5 RAEs, acute kidney injury (AKI), and grade 3-5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29-0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02-2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses. CONCLUSIONS: Among ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3-5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3-5 AKI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020197039.

16.
Front Med (Lausanne) ; 8: 619210, 2021.
Article in English | MEDLINE | ID: mdl-33937278

ABSTRACT

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury. Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results. Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017-1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316-8.986) and diabetes (OR = 2.522, 95%CI: 1.439-4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results. Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

17.
J Ren Nutr ; 31(6): 560-568.e2, 2021 11.
Article in English | MEDLINE | ID: mdl-33678546

ABSTRACT

OBJECTIVES: The aim of this study is to investigate the association between body composition, measured by bioelectrical impedance analysis, and outcomes in patients with acute kidney injury (AKI) receiving kidney replacement therapy (KRT). METHODS: Patients with severe AKI treated with KRT in our hospital between September 2016 and August 2018 were enrolled. These patients were assessed by body composition analysis before KRT, and on the 3rd day and the 7th day after initiation of KRT. The predictors included lean tissue index (LTI), fat tissue index, and body cell mass index (BCMI). The association between all-cause mortality and predictors was analyzed using Cox regression. RESULTS: A total of 152 patients were included in this study, with a 28-day mortality of 46.7% and 1-year mortality of 60.5%. LTI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.66, P < .001) and BCMI (adjusted hazard ratio per standard deviation: 0.37; 95% confidence interval = 0.21-0.67, P < .001) on day 7 after initiation of KRT, rather than before KRT, were associated with mortality during follow-up. LTI and BCMI before KRT were associated with 28-day mortality rather than 1-year mortality. CONCLUSIONS: LTI and BCMI before KRT were associated with short-term prognosis, and those on day 7 after KRT initiation were associated with intermediate mortality in patients with AKI requiring KRT.


Subject(s)
Acute Kidney Injury , Renal Dialysis , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Body Composition , Humans , Prognosis , Proportional Hazards Models , Renal Replacement Therapy
18.
Sci Rep ; 10(1): 10199, 2020 06 23.
Article in English | MEDLINE | ID: mdl-32576950

ABSTRACT

We compared the prognostic value of nutritional or volumetric parameters measured by body composition in hospitalized patients on maintenance hemodialysis. We conducted a cohort study to assess the association of different parameters of body composition with all-cause mortality in inpatients admitted to our nephrology department from January 2014 to December 2016. Of the 704 study patients, 160 (22.7%) died during a median follow-up of 33 months. In multivariate adjusted Cox models, higher ratio of extracellular water to body cell mass (ECW/BCM) (adjusted HR per 1-SD, 1.49; 95% CI, 1.19 to 1.85), lower lean tissue index (LTI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.57 to 0.86) and lower body cell mass index (BCMI) (adjusted HR per 1-SD, 0.70; 95% CI, 0.58 to 0.85) were associated with a significantly greater risk of death. When these parameters were added to the fully adjusted model, BCMI performed best in improving the predictability for all-cause mortality (integrated discrimination improvement = 0.02, P = 0.04; net reclassification index = 0.11, P = 0.04). Among body composition indexes, ECW/BCM was the most relevant fluid volume indices to mortality and BCMI and LTI were the most relevant nutritional status indices to mortality in maintenance hemodialysis patients.


Subject(s)
Body Composition/physiology , Renal Dialysis/mortality , Body Mass Index , Cohort Studies , Female , Follow-Up Studies , Hospital Mortality , Humans , Inpatients , Male , Middle Aged , Nutritional Status/physiology , Prognosis , Proportional Hazards Models , Risk Factors
19.
Clin Nephrol ; 94(2): 78-85, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32567543

ABSTRACT

OBJECTIVE: To determine the prognostic values of clinical and laboratory features at the time of presentation on renal function and survival of patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. (MPO-ANCA GN). MATERIALS AND METHODS: A total of 119 patients (52 males and 67 females) with MPO-ANCA GN and hospitalized at the First Affiliated Hospital of Nanjing Medical University from January 2010 to April 2018 were enrolled. The baseline clinical characteristics, renal biopsy pathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. RESULTS: Among these 119 patients, the median serum creatinine at diagnosis was 354.30 (range, 216.10 - 637.30) mmol/L and the median estimated glomerular filtration rate (eGFR) was 14.78 (range, 7.23 - 29.21) mL/min. In total, 58 (48.7%) patients received initial renal replacement therapy (RRT). During a median follow-up duration of 32 (range, 3 - 113) months, 57 (47.9%) patients progressed to end-stage renal disease (ESRD). Initial renal function status (i.e., initial RRT, serum creatinine, and eGFR) (p < 0.001) and hemoglobin level (p = 0.027) were significant risk factors for renal survival. During the follow-up, 69 (57.6%) of 119 patients survived. Age (p = 0.009) and urine red blood cell count (p = 0.012) were predictive of patient survival. CONCLUSION: Among patients with MPO-ANCA GN, poor renal function and lower hemoglobin level were predictive of ESRD, while older age and higher urinary red blood cell count were associated with a higher risk for all-cause mortality.


Subject(s)
Autoimmune Diseases , Glomerulonephritis , Antibodies, Antineutrophil Cytoplasmic , Autoimmune Diseases/epidemiology , Autoimmune Diseases/mortality , Autoimmune Diseases/physiopathology , Female , Glomerular Filtration Rate , Glomerulonephritis/epidemiology , Glomerulonephritis/mortality , Glomerulonephritis/physiopathology , Humans , Kidney/physiopathology , Male , Peroxidase , Retrospective Studies , Risk Factors
20.
Front Immunol ; 11: 607261, 2020.
Article in English | MEDLINE | ID: mdl-33613528

ABSTRACT

Objective: To determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN). Methods: A total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed. Results: All 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 µmol/L, p < 0.001), low albumin (<30 g/L, p = 0.024) and hemoglobin level (<90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (<30 g/L, p = 0.006) was significant risk factor for patient survival. Conclusion: Among patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Antibodies, Antineutrophil Cytoplasmic/blood , Glomerulonephritis/pathology , Kidney Glomerulus/pathology , Peroxidase/immunology , Age Factors , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/therapy , Biopsy , Disease Progression , Female , Glomerulonephritis/immunology , Glomerulonephritis/mortality , Glomerulonephritis/therapy , Glucocorticoids/therapeutic use , Hemoglobins/metabolism , Humans , Kidney Glomerulus/drug effects , Kidney Glomerulus/immunology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Renal Dialysis , Retrospective Studies , Risk Assessment , Risk Factors , Serum Albumin, Human/metabolism
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