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Microbiome Jun 2024The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal...
BACKGROUND
The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown.
RESULTS
A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated.
CONCLUSION
Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.
Topics: Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Dysbiosis; Gastrointestinal Microbiome; Inflammasomes; Mice; Rats; Hyperuricemia; Male; Disease Models, Animal; Kidney; Mice, Knockout; RNA, Ribosomal, 16S; Fecal Microbiota Transplantation; Urate Oxidase; Mice, Inbred C57BL
PubMed: 38907332
DOI: 10.1186/s40168-024-01826-9 -
Journal of Cardiovascular Imaging Jun 2024Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). In this study,...
BACKGROUND
Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). In this study, we estimated the prevalence of HF pre- and post-HD in ESRD using the current guidelines.
METHODS
We prospectively investigated HF in ESRD patients on HD using echocardiography pre- and post-HD. We used the structural and functional abnormality criteria of the 2021 European Society of Cardiology guidelines.
RESULTS
A total of 54 patients were enrolled. The mean age was 62.6 years, and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, and 20 (37.0%) had ischemic heart disease. The mean N-terminal-pro brain natriuretic peptide BNP (NT-proBNP) level was 12,388.8 ± 2,592.2 pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 min, and mean real filtration was 2.8 kg. The mean left ventricular ejection fraction (LVEF) was 62.4%, and mean left ventricular end-diastolic diameter was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower left atrial volume index (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), tricuspid regurgitation jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p < 0.001), and right ventricular systolic pressure (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There were no differences in LVEF, E/E' ratio, or left ventricular global longitudinal strain. A total of 88.9% of pre-HD patients and 66.7% of post-HD patients had either structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines (p = 0.007).
CONCLUSIONS
Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines. Pre-HD patients had a 22.2% higher incidence in the prevalence of functional or structural abnormalities as compared with post-HD patients.
PubMed: 38907294
DOI: 10.1186/s44348-024-00003-8 -
BMC Nephrology Jun 2024The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However,...
BACKGROUND
The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes.
CASE PRESENTATION
We present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction.
CONCLUSION
The simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.
Topics: Humans; Glomerulonephritis, Membranous; Male; Female; Middle Aged; Anti-Glomerular Basement Membrane Disease; Receptors, Phospholipase A2; Adult; Autoantibodies; Biopsy; Glomerulonephritis
PubMed: 38907217
DOI: 10.1186/s12882-024-03637-4 -
BMC Cancer Jun 2024The role of hemoglobin (HGB) in common malignant tumors remains unclear.
BACKGROUND
The role of hemoglobin (HGB) in common malignant tumors remains unclear.
METHODS
A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve.
RESULTS
High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05).
CONCLUSION
High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.
Topics: Humans; Retrospective Studies; Male; Female; Hemoglobins; Neoplasms; Genome-Wide Association Study; Prognosis; Middle Aged; Mendelian Randomization Analysis; Risk Factors; Nutrition Surveys; Adult; Aged; Biomarkers, Tumor
PubMed: 38907210
DOI: 10.1186/s12885-024-12495-0 -
BMC Nephrology Jun 2024IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis... (Review)
Review
IgA nephropathy, presently recognized as the foremost primary glomerular disorder, emerges as a principal contributor to renal failure globally, with its pathogenesis yet to be fully elucidated. Extensive research has highlighted the critical role of gut microbiome in the onset and progression of IgA nephropathy, underscoring its importance in accurately delineating the disease's etiology. For example, gut microbiome dysbacteriosis can lead to the production of nephritogenic IgA1 antibodies, which form immune complexes that deposit in the kidneys, causing inflammation and damage. The gut microbiome, a source of numerous bioactive compounds, interacts with the host and plays a regulatory role in gut-immune axis modulation, earning it the moniker of the "second brain." Recent investigations have particularly emphasized a significant correlation between IgA nephropathy and gut microbiome dysbacteriosis. This article offers a detailed overview of the pathogenic mechanisms of IgA nephropathy, specifically focusing on elucidating how alterations in the gut microbiome are associated with anomalies in the intestinal mucosal system in IgA nephropathy. Additionally, it describes the possible influence of gut microbiome on recurrent IgA nephropathy following kidney transplantation. Furthermore, it compiles potential therapeutic interventions, offering both theoretical and practical foundations for the management of IgA nephropathy. Lastly, the challenges currently faced in the therapeutic approaches to IgA nephropathy are discussed.
Topics: Glomerulonephritis, IGA; Humans; Gastrointestinal Microbiome; Dysbiosis; Immunity, Mucosal; Intestinal Mucosa; Kidney Transplantation
PubMed: 38907188
DOI: 10.1186/s12882-024-03646-3 -
Discover Oncology Jun 2024Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently...
BACKGROUND
Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood.
METHODS
The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature.
RESULTS
A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents.
CONCLUSIONS
The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.
PubMed: 38904744
DOI: 10.1007/s12672-024-01105-x -
World Journal of Urology Jun 2024Current potential living kidney donor's assessment includes functional and anatomical evaluation. Scintigraphy is recommended in some cases and some centers include this...
BACKGROUND
Current potential living kidney donor's assessment includes functional and anatomical evaluation. Scintigraphy is recommended in some cases and some centers include this test in the donor's protocol. Recent studies advocate for the avoidance of this test as CT or MRI volumetry showed to accurately assess donor's renal function.
OBJECTIVE
To summarize scientific evidence on image tests for pre-donation and/or post-nephrectomy renal function evaluation.
EVIDENCE ACQUISITION
This review followed the guidelines set by the European Association of Urology and adhered to PRISMA 2020 recommendations. The protocol was registered in PROSPERO on 10th December 2022 (ID: CRD42022379273).
EVIDENCE SYNTHESIS
Twenty-one studies met the inclusion criteria after thorough screening and eligibility assessment. According to QUADAS-2, patient selection and flow/timing domains showed a predominant low risk of bias. The correlation between split renal function (SRF) using CT and scintigraphy varied from weak (r = 0.21) to remarkably strong (r = 0.949). Bland-Altman agreement demonstrated moderate to excellent results, with mean differences ranging from -0.06% to 1.76%. The correlation between split renal volume (CT) and estimated glomerular filtration rate (eGFR) at 6 months or 1 year after nephrectomy showed a moderate correlation, with coefficients ranging from 0.708 to 0.83. The correlation between SRF (MRI) and renal scintigraphy reported a moderate correlation, with correlation coefficients of 0.58 and 0.84. MRI and scintigraphy displayed a good agreement, with a 66% agreement observed and mean differences of ± 0.3%.
CONCLUSIONS
Despite study heterogeneity, MRI or CT-based renal volumetry appears promising compared to scintigraphy, with favorable correlations and agreement.
Topics: Humans; Living Donors; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Radionuclide Imaging; Kidney Transplantation; Nephrectomy; Kidney; Kidney Function Tests; Tissue and Organ Harvesting
PubMed: 38904679
DOI: 10.1007/s00345-024-05024-y -
JACC. Heart Failure Jun 2024Although some patients with heart failure (HF) with mildly reduced/preserved ejection fraction have low natriuretic peptide levels, there are no large-scale systematic...
BACKGROUND
Although some patients with heart failure (HF) with mildly reduced/preserved ejection fraction have low natriuretic peptide levels, there are no large-scale systematic studies of how common these individuals are or what happens to them.
OBJECTIVES
The purpose of this study was to examine the proportion of patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction) trial with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level <125 pg/mL, their clinical characteristics, and outcomes.
METHODS
I- PRESERVE enrolled patients with symptomatic HF and a LVEF ≥45% but who did not have NT-proBNP or body mass index inclusion/exclusion criteria. Baseline NT-proBNP was measured after enrollment but not reported to investigators. The primary outcome in this analysis was the composite of cardiovascular death or HF hospitalization.
RESULTS
Overall, 808 of 3,480 patients (23.2%) had NT-proBNP <125 pg/mL. Patients with a low NT-proBNP were younger (68.6 years vs 72.6 years; P < 0.001), were less often men (36.1% vs 40.9%; P = 0.015), and had a higher body mass index (48.4% vs 38.7% obese; P < 0.001) than those with a higher NT-proBNP level. Patients with a low NT-proBNP had less atrial fibrillation (8.5% vs 35.1%; P < 0.001), myocardial infarction, diabetes, chronic obstructive pulmonary disease, and anemia but better kidney function. Patients with a lower NT-proBNP level had less marked echocardiographic abnormalities and were less likely to experience cardiovascular death or HF hospitalization; adjusted HR: 0.35 (95% CI: 0.27-0.46; P < 0.001). However, health status was similarly impaired in patients with lower and higher NT-proBNP levels (median Minnesota Living with Heart Failure Questionnaire 43 vs 43; P = 0.95).
CONCLUSIONS
Almost one-quarter of patients with HF with mildly reduced/preserved ejection fraction had a low NT-proBNP level. Although these patients have a favorable prognosis, compared to those with a high NT-proBNP level, they have similarly impaired health status which should be a target for treatment. (Irbesartan in Heart Failure With Preserved Systolic Function [I- PRESERVE]; NCT00095238).
PubMed: 38904646
DOI: 10.1016/j.jchf.2024.04.027 -
JACC. Clinical Electrophysiology May 2024Cardiac troponins (cTns) and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk...
BACKGROUND
Cardiac troponins (cTns) and biomarkers of inflammation are elevated in heart failure (HF) and predict cardiovascular risk. Whether these biomarkers associate with risk of ventricular arrhythmias (VAs) is unclear.
OBJECTIVES
This study sought to assess whether cTnT, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations are associated with incident VA.
METHODS
In a prospective, observational study of patients treated with implantable cardioverter-defibrillator, cTnT, GDF-15, IL-6, and CRP were measured at baseline and after 1.4 ± 0.5 years and were associated with implantable cardioverter-defibrillator-detected incident VA, HF hospitalizations, and mortality.
RESULTS
This study included 489 patients aged 66 ± 12 years and 83% were men. Median concentrations of cTnT were 15 (Q1-Q3: 9-25) ng/L at inclusion, and higher concentrations were associated with higher age, male sex, diabetes mellitus, coronary artery disease, and HF. During 3.1 ± 0.7 years of follow-up, 137 patients (28%) had ≥1 VA. cTnT concentrations were associated with an increased VA risk (per log-unit, HR: 1.63; 95% CI: 1.31-2.01; P < 0.001), also after adjustment for age, sex, body mass index, coronary artery disease, HF, renal function, and left ventricular ejection fraction (P < 0.001). GDF-15, IL-6, and CRP concentrations were not associated with incident VA, but all (including cTnT) were associated with HF hospitalization and mortality. Changes in cTnT, GDF-15, IL-6, and CRP from baseline to 1.4 years were not associated with subsequent VA.
CONCLUSIONS
Higher concentrations of cTnT, GDF-15, IL-6, and CRP associate with HF hospitalization and death, but only cTnT predict incident VA. These findings suggest that myocardial injury rather than inflammation may play a pathophysiological role in VA and sudden cardiac death.
PubMed: 38904572
DOI: 10.1016/j.jacep.2024.04.017 -
Iranian Journal of Kidney Diseases May 2024Ambulatory blood pressure monitoring (ABPM) is a valuable tool for detecting abnormalities in nighttime blood pressure (BP), including non-dipping and nighttime...
INTRODUCTION
Ambulatory blood pressure monitoring (ABPM) is a valuable tool for detecting abnormalities in nighttime blood pressure (BP), including non-dipping and nighttime hypertension. These abnormalities are independent predictors of a poor prognosis in patients with chronic kidney disease (CKD). The aim of our study was to analyze ABPM data and evaluate nighttime BP abnormalities in an Iranian CKD population.
METHODS
This cross-sectional study was conducted on sixty two patients at stages III and IV of CKD who were referred to a nephrology clinic in Tehran, Iran. The patients were classified as either dippers (19.4%) or non-dippers (80.6%), as well as nighttime normotensives (38.7%) or hypertensives (61.3%), based on ABPM data and in accordance with 2023 ESC/ESH guidelines. We compared demographic data, estimated glomerular filtration rate (eGFR), and daytime BP levels among these groups.
RESULTS
The mean age of patients was 56.34 years, with 61.1% of them being male. Daytime pulse pressure was significantly greater in non-dippers compared to dippers (52.67 vs. 44 mmHg, P = .02). We found a significant correlation between the extent of BP dipping and eGFR (R = 0.281, P = .02). Systolic and diastolic daytime BP levels were significantly higher in individuals with nighttime hypertension. Diabetic patients were more likely to be non-dippers and have nighttime hypertension. After adjusting for age, diabetes mellitus, and daytime pulse pressure in a multivariable model, we determined that eGFR independently predicted the extent of BP dipping.
CONCLUSION
Our results showed that both non-dipping and nighttime hypertension are highly prevalent in CKD patients, but they have distinct contributing factors. The eGFR was identified as an independent predictor of BP dipping, whereas nighttime BP levels were primarily determined by daytime BP levels. DOI: 10.52547/ijkd.7559.
Topics: Humans; Male; Blood Pressure Monitoring, Ambulatory; Female; Middle Aged; Cross-Sectional Studies; Iran; Renal Insufficiency, Chronic; Hypertension; Circadian Rhythm; Glomerular Filtration Rate; Blood Pressure; Aged; Adult; Risk Factors
PubMed: 38904341
DOI: 10.52547/q4b5rx79