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.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Objective: Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. Methods: This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Results: Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. Conclusions: The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.

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.

Risk Factors for Progression of CKD with and without Diabetes.

Objective: We aim to identify independent risk factors to predict CKD progression to end stage renal disease (ESRD) in patients with or without diabetes. Methods: In this retrospective study, we enrolled CKD stage 3-4 patients between January 2013 and December 2018 and followed them until December 2020 or the initiation of dialysis. We used Kaplan-Meier to plot the survival curve. Univariate and multivariable Cox proportional hazards model was used to explore risk factors affecting the progression of CKD. The final model was used to construct nomogram for predicting CKD progression. Calibration plots and concordance index (C-index) were used to evaluate the accuracy and discrimination of the risk model. Results: We enrolled 309 CKD patients, including 80 cases in G3a, 98 cases in G3b, and 131 cases in G4. Among them, 141 patients had diabetes and 168 did not. The mean age of patients at enrolled was 57.86 ± 15.10 years, and 67% were male. The median follow-up time was 25.6 months. There were 81 patients (26.2%) that started dialysis in the total CKD cohort, 52 cases (36.9%) in the CKD with diabetes group, and 29 cases (17.3%) in the CKD without diabetes group. Hypoalbuminemia (HR =2.655, P < 0.001), proteinuria (HR =2.592, P = 0.042), increased LDL (HR =2.494, P < 0.001), diabetes (HR =2.759, P < 0.001), hypertension (HR =3.471, P = 0.037), and CKD stage (HR =2.001, P = 0.046) were risk factors for CKD progression to ESRD in the overall population. For those without diabetes, only hypoalbuminemia (HR =2.938, P = 0.030) was a risk factor for CKD progression to ESRD. For those with diabetes, both hypoalbuminemia (HR =2.758, P = 0.002), the increased level of LDL (HR =3.982, P < 0.001), and CKD stage (HR =3.781, P = 0.001) were risk factors for CKD progression to ESRD. The C-index of the final nomograms was 0.760 (P < 0.001). Conclusions: The results from our risk factor model suggest that CKD disease progression can be predicted and early strategic intervention is necessary for CKD patients to avoid renal function deterioration.

Berberine improves neurogenic contractile response of bladder detrusor muscle in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptidis Rhizoma has been used to treat diabetes mellitus for more than 1400 years in China. Berberine, one of the main alkaloids of Coptidis Rhizoma, is a principal antidiabetic component of Coptidis Rhizoma. To investigate the effects of berberine on impaired neurogenic contractility of detrusor muscle from urinary bladder of rats with early stage diabetes. MATERIALS AND METHODS: The detrusor muscle strips were isolated from urinary bladders of streptozotocin-induced diabetic rats, 5% sucrose-induced diuretic rats or normal rats, and were placed in organ bath. The contractions induced by electrical field stimulation (EFS), carbachol, KCl, adenosine triphosphate, and the effects of berberine on those contractions were measured. RESULTS: The EFS- or KCl-induced contraction of detrusor muscle was significantly decreased in diabetic rats as compared with diuretic or normal rats. Atropine and suramin inhibited EFS-induced contraction. In diabetic rats, the atropine sensitive components were decreased in EFS-induced contraction of detrusor muscle, and the adenosine triphosphate-induced contraction was significantly increased. The carbachol-induced contrations were not different among groups. Berberine significantly potentiated EFS-induced contractions of detrusor muscle both from normal and diabetic rats, but the potentiated effect of BBR was more sensitive to atropine in diabetic rats. Berberine also potentiated adenosine triphosphate-induced contraction of detrusor muscle, but did not change carbachol- or KCl-induced contraction. CONCLUSION: The neurogenic contraction of urinary bladder detrusor muscle is decreased while purinergic contraction of bladder detrusor muscle is increased in rats with early stage diabetes. Berberine increases the neurogenic contractile response to EFS possibly via both presynaptic increasing neurotransmitters release and postsynaptic potentiation of purinergic transmitter-regulated response in rat urinary bladder detrusor; and in diabetic rats, berberine increases neurogenic contractile response mainly via the presynaptic increasing acetylcholine release.