Correlation between coronary calcification and cardiac structure in non-dialysis patients with chronic kidney disease.

AIMS: We aim to explore the correlation between coronary artery calcification (CAC) score (CACS) and cardiac structure and function in chronic kidney disease (CKD) patients, create a clinical prediction model for severe CAC associated with cardiac ultrasound indexes. METHODS AND RESULTS: The study included 178 non-dialysis CKD patients who underwent CACS testing and collected general information, serological indices, cardiac ultrasound findings and follow-up on renal function, heart failure (HF) manifestations and re-hospitalization. The mean age of participants in the study cohort was 67.4 years; 59% were male, and 66.9% of patients had varying degrees of comorbid CAC. CKD patients with CACS > 100 were older, predominantly male and had a higher proportion of smoking, diabetes and hypertension (P < 0.05) compared with those with CACS = 0 and 0 < CACS ≤ 100, and had higher brain natriuretic peptide, serum magnesium and fibrinogen levels were also higher (P < 0.05). CACS was positively correlated with left atrial inner diameter (LAD), left ventricular end-diastolic inner diameter (LVDd), left ventricular volume at diastole (LVVd), output per beat (SV) and mitral orifice early diastolic blood flow velocity/early mitral annular diastolic myocardial motion velocity (E/e) (P < 0.05). We tested the associations between varying degrees of CAC and HF and heart valve calcification using multivariable-adjusted regression models. The risk of HF in patients with severe CAC was about 1.95 times higher than that in patients without coronary calcification, and the risk of heart valve calcification was 2.46 times higher than that in patients without coronary calcification. Heart valve calcification and HF diagnosis, LAD and LVDd are essential in predicting severe CAC. During a mean follow-up time of 18.26 ± 10.17 months, 65 (36.52%) patients had a composite renal endpoint event, of which 36 (20.22%) were admitted to renal replacement therapy. Patients with severe CAC had a higher risk of progression of renal function, re-admission due to cardiovascular and renal events and more pronounced symptoms of HF (P < 0.05). CONCLUSIONS: There is a correlation between CACS and cardiac structure and function in non-dialysis CKD patients, which may mainly involve abnormalities in left ventricular structure and cardiac diastolic function. CAC may affect renal prognosis and quality of survival in CKD patients. Based on clinical information, HF, valvular calcification status and indicators related to left ventricular hypertrophy can identify people at risk for severe CAC.

Identification and validation of voltage-dependent anion channel 1-related genes and immune cell infiltration in diabetic nephropathy.

AIMS/INTRODUCTION: This study investigated the roles of voltage-dependent anion channel 1-related differentially expressed genes (VRDEGs) in diabetic nephropathy (DN). MATERIALS AND METHODS: We downloaded two datasets from patients with DN, namely, GSE30122 and GSE30529, from the Gene Expression Omnibus database. VRDEGs associated with DN were obtained from the intersection of voltage-dependent anion channel 1-related genes from the GeneCards database, and differentially expressed genes were screened according to group (DN/healthy) in the two datasets. The enriched pathways of the VRDEGs were analyzed. Hub genes were selected using a protein-protein interaction network, and their predictive value was verified through receiver operating characteristic curve analysis. The CIBERSORTx software examined hub genes and immune cell infiltration associations. The protein expression of hub genes was verified through immunohistochemistry in 16-week-old db/db mice for experimentation as a model of type 2 DN. Finally, potential drugs targeting hub genes that inhibit DN development were identified. RESULTS: A total of 57 VRDEGs were identified. The two datasets showed high expression of the PI3K, Notch, transforming growth factor-ß, interleukin-10 and interleukin-17 pathways in DN. Five hub genes (ITGAM, B2M, LYZ, C3 and CASP1) associated with DN were identified and verified. Immunohistochemistry showed that the five hub genes were highly expressed in db/db mice, compared with db/m mice. The infiltration of immune cells was significantly correlated with the five hub genes. CONCLUSIONS: Five hub genes were significantly correlated with immune cell infiltration and might be crucial to DN development. This study provides insight into the mechanisms involved in the pathogenesis of DN.

Complement C3 mediates podocyte injury through TLR4/NFΚB-P65 signaling during ischemia-reperfusion acute kidney injury and post-injury fibrosis.

BACKGROUND: The aim of this study was to explore the mechanism of complement C3a mediating podocyte injury during ischemia-reperfusion acute kidney injury (IR-AKI) and post-injury fibrosis. METHODS: Renal artery clamping was used to establish IR-AKI and post-injury fibrosis model. HE and Masson staining were performed to observe renal fibrosis. The protein abundance levels were measured along with inflammatory markers, renal complement C3. Podocytes were treated with C3a with or without Toll-like receptor 4(TLR4) inhibitor. The effects of TLR4 up-regulation by TLR4 plasmids were examined. RESULTS: C3-/- resulted in amelioration of renal dysfunction by reducing podocyte damage and renal fibrosis. Immunoblot with renal tissue homogenates from IR-AKI mice revealed that C3-/- decreased TLR4/Nuclear Factor-κB (NFκB)-P65. CONCLUSION: Our results indicate that modulating C3/TLR4/NFκB-P65 signaling pathway is a novel therapeutic target for the IR-AKI and post-injury fibrosis.

Association of Red Blood Cell Life Span with Abnormal Changes in Cardiac Structure and Function in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.

Introduction: With the invention and improvement of the carbon monoxide (CO) breath test, the role of shortened red blood cell life span (RBCLS) in renal anemia, an independent risk factor for cardiovascular events in patients with chronic kidney disease (CKD), is gradually attracting attention. Considering that heart failure is the leading cause of morbidity and mortality in patients with CKD, this study investigated the correlation between the RBCLS and the cardiac structure and function in non-dialysis patients with CKD stages 3−5, aiming to provide new ideas to improve the long-term prognosis of CKD patients. Methods: One hundred thirty-three non-dialysis patients with CKD stages 3−5 were tested for RBCLS. We compared the serological data, cardiac ultrasound results, and follow-up prognosis of patients with different RBCLS. Results: As the RBCLS shortened, the patients' blood pressure, BNP, and CRP gradually increased, most significantly in patients with an RBCLS < 50 d. Patients with an RBCLS < 50 d had substantially lower hemoglobin (Hb), hematocrit, and albumin levels than those with an RBCLS ≥ 50 d. The cardiac ultrasound results show that patients with an RBCLS < 50 d had significantly larger atrial diameters than those with an RBCLS ≥ 50 d and were associated with more severe diastolic dysfunction. Patients with an RBCLS < 50 d had a 3.06 times greater risk of combined heart failure at baseline than those with an RBCLS ≥ 70 d and a higher risk of heart failure at follow-up. CKD stage 5 patients with an RBCLS < 50 d were more likely to develop heart failure and require renal replacement therapy earlier than patients with an RBCLS ≥ 50 d. Conclusions: In non-dialysis patients with CKD stages 3−5, there is a correlation between the red blood cell life span and cardiac structure and function. The RBCLS may also impact the renal prognosis of CKD patients.