The relationship between dietary inflammatory index (DII) and early renal injury in population with/without hypertension: analysis of the National health and nutrition examination survey 2001-2002.

BACKGROUND: Inflammation plays a crucial role in occurrence of kidney injury, and specific dietary patterns can influence systemic inflammation levels. However, the relationship between dietary inflammatory potential and early-stage kidney damage remains unclear. METHOD: 2,108 participants was recruited from 2001-2002 National Health and Nutrition Examination Survey (NHANES). Dietary Inflammatory Index (DII) is utilized to assess dietary inflammatory potential, calculated through a 24-h dietary recall questionnaire. Early renal injury was evaluated using urinary albumin to creatinine (UACR), cystatin C (CysC), ß-2 microglobulin (ß2M), and estimated glomerular filtration rate (eGFR) based on serum creatinine (eGFRs), cystatin C (eGFRc), and both Scr and CysC (eGFRs&c). Participant characteristics were analyzed, and association between DII, hypertension, and early renal injury markers was explored using multiple linear and logistic regression models. RESULTS: The average age of participants was 53.9 years. DII exhibited a positive correlation with UACR (ß = -0.048[0.017,0.078]), ß2M (ß = 0.019[0.010,0.027]), CysC (ß = 0.012 [0.004,0.021]). Conversely, a negative correlation was observed between DII and eGFRc (ß = -1.126[-1.554, -0.699]), eGFRs&c (ß=-1.101[-1.653, -0.549]). A significant association was observed between hypertension and abnormality of early kidney damage markers. Subgroup analysis reveals that the positive correlation between DII and the occurrence of abnormal markers of early kidney damage is only observed in individuals with hypertension. Furthermore, an interaction between DII and hypertension was detected in eGFRs&c (OR:1.250[1.042, 1.499], p for interaction = 0.03). CONCLUSION: Higher levels of DII may be associated with occurrence of early kidney damage. For individuals with hypertension, avoiding excessive consumption of pro-inflammatory foods may reduce the risk of renal injury.

Bioinformatics-driven discovery of silica nanoparticles induces apoptosis and renal damage via the unfolded protein response in NRK-52E cells and rat kidney.

Silica nanoparticles (SiNPs) are nanomaterials with widespread applications in drug delivery and disease diagnosis. Despite their utility, SiNPs can cause chronic kidney disease, hindering their clinical translation. The molecular mechanisms underlying SiNP-induced renal toxicity are complex and require further investigation. To address this challenge, we employed bioinformatics tools to predict the potential mechanisms underlying renal damage caused by SiNPs. We identified 1627 upregulated differentially expressed genes (DEGs) and 1334 downregulated DEGs. Functional enrichment analysis and protein-protein interaction network revealed that SiNP-induced renal damage is associated with apoptosis. Subsequently, we verified that SiNPs induced apoptosis in an in vitro model of NRK-52E cells via the unfolded protein response (UPR) in a dose-dependent manner. Furthermore, in an in vivo rat model, high-dose SiNP administration via tracheal drip caused hyalinization of the renal tubules, renal interstitial lymphocytic infiltration, and collagen fiber accumulation. Concurrently, we observed an increase in UPR-related protein levels at the onset of renal damage. Thus, our study confirmed that SiNPs induce apoptosis and renal damage through the UPR, adding to the theoretical understanding of SiNP-related kidney damage and offering a potential target for preventing and treating kidney injuries in SiNP clinical applications.

Association of dietary inflammatory index with all-cause and cardiovascular disease mortality in hyperuricemia population: A cohort study from NHANES 2001 to 2010.

Dietary management is a crucial component of non-pharmacological treatment for hyperuricemia, yet there is a paucity of research on the impact of dietary habits on the survival outcomes of individuals with hyperuricemia. The objective of this study is to examine the association between dietary inflammatory index (DII) and the all-cause and cardiovascular disease (CVD) mortality in individuals with hyperuricemia. This study included 3093 adult participants from National Health and Nutrition Examination Survey (NHANES) 2001 to 2010. Participants were categorized into 4 groups based on quartiles of DII to demonstrate data characteristics, with sample weights considered. The relationship between DII and the risk of hyperuricemia was examined using multivariable logistic regression models. Kaplan-Meier models and Cox proportional hazards models were employed to assess the relationship between DII levels and the all-cause mortality in individuals with hyperuricemia, with the non-linear relationship tested using restricted cubic splines (RCS). Competing risk models were employed to investigate the association between DII levels and the CVD mortality in individuals diagnosed with hyperuricemia. Subgroup and sensitivity analysis were performed to confirm the robustness and reliability of the findings. Among the participants, 47.95% were aged over 60 years. A positive association observed between the highest quartile of DII level and the incidence of hyperuricemia (OR: 1.34, CI [1.13, 1.57]). Elevated DII levels were correlated with increased all-cause mortality (P value < .001) and CVD mortality (P value < .001) in participants. In comparison to the lowest quartile, the highest quartile of DII exhibited a 31% rise in all-cause mortality (HR: 1.31, CI [1.01, 1.68]) and a 50% increase in CVD mortality (HR: 1.50, CI [1.00, 2.26]). No indication of a nonlinear association between DII levels and all-cause mortality (p-non-linear = .43). These findings indicate a positive correlation between the pro-inflammatory diet and the incidence of hyperuricemia. Additionally, a pro-inflammatory diet may elevate the all-cause and CVD mortality in individuals with hyperuricemia.

Effect of dietary protein intake on cognitive function in the elderly with chronic kidney disease: analysis of the National Health and Nutrition Examination Survey 2011-2014.

BACKGROUND: Cognitive dysfunction is prevalent among the elderly diagnosed with chronic kidney disease (CKD). Low protein diets are used for retarding the progression of CKD in clinical practice. Nonetheless, the impact of dietary protein consumption on cognitive function in this population remains uncertain. METHODS: We recruited 2306 participants (≥60 years) from 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). 24-h dietary recall questionnaire was utilized to evaluate protein intake. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Participants' characteristics were analyzed, and the interaction between protein consumption and CKD on cognitive impairment were analyzed using a logistic regression model. RESULTS: We divided participants into three groups based on CKD stages: no CKD, CKD stage G1 to G2 (19%), and CKD stage G3 to G5 (18%). The average protein intake was 0.97 g/(kg·d). In the higher protein intake group, CKD stages G1 to G2 elevated the risk of immediate memory impairment (OR: 2.441, 95% Cl: 1.161-5.132 for protein consumption in 1.0-1.2g/(kg·d); OR: 2.225, 95% Cl: 1.015-4.876 for protein consumption in >1.2 g/(kg·d)). However, no similar resuts were observed in the lower protein intake group. In addition, the interaction between CKD status and protein intake on immediate memory was statistically significant (p = .041). CONCLUSION: A higher probability of cognitive impairment in the elderly with early-stage CKD may be linked to higher protein intake. Low protein diets may be a potential strategy to release cognitive impairment in the elderly with early-stage CKD.

Pegmolesatide for the treatment of anemia in patients undergoing dialysis: a randomized clinical trial.

Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18-70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ -1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and -0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11-0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

AIDS with obesity, hypothyroidism and elevated serum creatinine: A case report.

Hypothyroidism is a prevalent endocrine illness with a variety of clinical symptoms, but among which elevated serum creatinine is uncommon. Hypothyroidism is also common in acquired immunodeficiency syndrome (AIDS) patients, especially those receiving highly active antiretroviral treatment (HAART). Here we present a case of a young AIDS patient with hypothyroidism, increased serum creatinine, and obesity. Despite the lack of a kidney biopsy, following levothyroxine (LT4) therapy, his serum creatinine recovered to normal levels, and weight loss, edema, weakness, rough skin and other clinical symptoms obtained notable improvement. This highlights the need of clinicians paying attention to whether thyroid function is aberrant in human immunodeficiency virus (HIV) patients with increased creatinine, edema and significant weight gain since prompt thyroid hormone therapy can restore the alterations in renal function and avoid invasive renal biopsy.

Novel insights into modifiable risk factors for arteriovenous fistula failure and the importance of CKD lipid profile: A meta-analysis.

BACKGROUND: Arteriovenous fistula (AVF) failure can occur in patients undergoing hemodialysis (HD). In this study, we explored the correlation between hyperlipidemia and AVF failure in patients undergoing HD. Moreover, we compared the lipid profiles of patients with chronic kidney disease (CKD) with those of healthy people to provide a basis for lipid-lowering in patients undergoing HD. METHOD AND ANALYSIS: We searched PubMed, Web of Science, Embase, the Cochrane library, CNKI, CBM, the China Science Periodical Database, and the China Science and Technology Journal Database. The final search was conducted on August 31, 2021, and the search period was restricted between 2000 and August 31, 2021, without publication restrictions. All studies met the inclusion criteria, and the influences of sex, age, geographical location, diagnosis method, and publication year were excluded. The data were analyzed using the random-effects model and the fixed-effects model. RESULTS: Twenty-eight studies were included in the meta-analysis with 121,666 patients in the CKD group and 1714 patients in the AVF failure group. Triglyceride concentration in patients with CKD was higher than in healthy subjects (MD: -31.56, 95% CI: -41.23 to -21.90, p < 0.00001). A high total cholesterol (TC) concentration (MD: 6.97, 95% CI: 2.19-11.74, p = 0.004) and a high low-density lipoprotein cholesterol (LDL-C) concentration (MD: 23.83, 95% CI: 18.48-29.18, p < 0.00001) were associated with AVF failure. Furthermore, HDL-C was lower in the AVF failure group than in the AVF patency group (MD: -2.68, 95% CI: -4.60 to -0.76, p = 0.006). CONCLUSION: Our analysis indicates that the AVF failure may be related to the increase of TC/LDL-C and the decrease of HDL-C. Although current guidelines do not consider intensive lipid-lowering therapy as necessary in patients undergoing HD, our research indicates that patients with AVF undergoing HD may need regular TC/LDL-C-lowering therapy to prevent AVF failure. However, this issue still needs well designed prospective trials.

Computational study of effective matrix metalloproteinase 9 (MMP9) targeting natural inhibitors.

OBJECT: The present study screened ideal lead natural compounds that could target and inhibit matrix metalloproteinase 9 (MMP9) protein from the ZINC database to develop drugs for clear cell renal cell carcinoma (CCRCC)-targeted treatment. METHODS: Discovery Studio 4.5 was used to compare and screen the ligands with the reference drug, solasodine, to identify ideal candidate compounds that could inhibit MMP9. The LibDock module was used to analyze compounds that could strongly bind to MMP9, and the top 20 compounds determined by the LibDock score were selected for further research. ADME and TOPKAT modules were used to choose the safe compounds from these 20 compounds. The selected compounds were analyzed using the CDOCKER module for molecular docking and feature mapping for pharmacophore prediction. The stability of these compound-MMP9 complexes was analyzed by molecular dynamic simulation. Cell counting kit-8, colony-forming, and scratch assays were used to analyze the anti-CCRCC effects of these ligands. RESULTS: Strong binding to MMP9 was exhibited by 6,762 ligands. Among the top 20 compounds, sappanol and sventenin exhibited nearly undefined blood-brain barrier level and lower aqueous solubility, carcinogenicity, and hepatotoxicity than the positive control drug, solasodine. Additionally, these compounds exhibited lower potential energies with MMP9, and the ligand-MMP9 complexes were stable in the natural environment. Furthermore, sappanol inhibited CCRCC cell migration and proliferation. CONCLUSION: Sappanol and sventenin are safe and reliable compounds to target and inhibit MMP9. Sappanol can CCRCC cell migration and proliferation. These two compounds may give new thought to the targeted therapy for patients with CCRCC.

Identification of key genes, pathways and potential therapeutic agents for IgA nephropathy using an integrated bioinformatics analysis.

PURPOSE: This study aims to identify immunoglobulin-A-nephropathy-related genes based on microarray data and to investigate novel potential gene targets for immunoglobulin-A-nephropathy treatment. METHODS: Immunoglobulin-A-nephropathy chip data was obtained from the Gene Expression Omnibus database, which included 10 immunoglobulin-A-nephropathy and 22 normal samples. We used the limma package of R software to screen differentially expressed genes in immunoglobulin-A-nephropathy and normal glomerular compartment tissues. Functional enrichment (including cellular components, molecular functions, biological processes) and signal pathways were performed for the differentially expressed genes. The online analysis database (STRING) was used to construct the protein-protein interaction networks of differentially expressed genes, and Cytoscape software was used to identify the hub genes of the signal pathway. In addition, we used the Connectivity Map database to predict possible drugs for the treatment of immunoglobulin-A-nephropathy. RESULTS: A total of 348 differentially expressed genes were screened including 107 up-regulated and 241 down-regulated genes. Functional analysis showed that up-regulated differentially expressed genes were mainly concentrated on leukocyte migration, and the down-regulated differentially expressed genes were significantly enriched in alpha-amino acid metabolic process. A total of six hub genes were obtained: JUN, C3AR1, FN1, AGT, FOS, and SUCNR1. The small-molecule drugs thapsigargin, ciclopirox and ikarugamycin were predicted therapeutic targets against immunoglobulin-A-nephropathy. CONCLUSION: Differentially expressed genes and hub genes can contribute to understanding the molecular mechanism of immunoglobulin-A-nephropathy and providing potential therapeutic targets and drugs for the diagnosis and treatment of immunoglobulin-A-nephropathy.

Genetic and functional analysis of two missense mutations in CD46 predispose to postpartum atypical hemolytic uremic syndrome.

Pregnancy associated atypical hemolytic uremic syndrome (p-aHUS) is a disease with a triad of hemolytic anemia, thrombocytopenia and acute renal failure, which might be attributed to the uncontrolled complement activation. Herein, we sequenced a postpartum-aHUS patient and found the two missense variants of CD46, a novel mutation (c.403G > C, p.G135R) from her father and a once reported mutation (c.293C > T, p.T98I) without expressional and functional tests from her mother. The G135R mutation caused a significantly reduced membrane expression of CD46 in peripheral blood lymphocyte and renal cells. The T98I mutation caused a mild decrease membrane expression of CD46 in peripheral blood lymphocyte cells. Moreover, the expressed G135R protein was in precursor form, indicating that this mutant was retained intracellularly. The C3b binding ability of T98I mutant was slightly decreased while the C4b binding ability is not significantly changed. The cofactor ability of the two mutants for factor I in the degradation of C3b was demonstrated to be impaired. This study reported the first case of a four-generation postpartum-aHUS pedigree with isolated CD46 variants and the detailed disease progression, treatment, and prognosis provided more meaningful information for the understanding the disease.

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.

[One Case about Primary Pulmonary Squamous Cell Carcinoma 
with Retinal Metastasis].

Lung cancer is a common malignant tumor in clinic. Morbidity and mortality are the first place in cancer, which seriously threaten the health of human beings. Due to the lack of effective and specific screening methods, most patients were found already at an advanced stage, and often combined with bone, brain, liver, adrenal and other parts of the metastasis. Symptoms of patient resulted from the primary tumor, metastatic spread, or paraneoplastic syndrome commonly cause the medical attention. For the syndrome related to the distant metastatic spread as the first manifestation, diagnosis would be a challenge. Retinal metastasis is very rare as the first symptom of squamous cell carcinoma of the lung. This paper reviewed a case, in which a patient developed the retinal metastasis as the inital presentation. After systemic evaluation, our patient was managed in multidisciplinary treatments, including surgery and chemotherapy. Now, the patient has a good short-term prognosis and is still in fellow-up condition. Later, we summarized the characteristics of the diagnosis and treatment of this case and provided experience for clinicians. At the same time, reviewing the relevant literature on tumor metastasis provides a window for our understanding of the rare manifestations of lung cancer.