[Ambulatory arterial stiffness index and associated factors in patients with diabetic kidney disease].

OBJECTIVE: To compare arterial stiffness between diabetic kidney disease and non-diabetic kidney diseaseand to identify factors predicting ambulatory arterial stiffness index (AASI). METHODS: Forty-four patients with diabetic kidney disease (DKD group) and thirty-one patients with non-diabetic kidney disease (NDKD group) were recruited for this study. All of the participants had hypertension. The AASI (indirect reflex global arterial stiffness)and short-term blood pressure variability (BPV) were measured using a 24-h ambulatory BP monitoring, and compared.between DKD and NDKD groups using analyses of covariance, correlation analysis and multivariate linear regression model. RESULTS: DKD patients had significantly higher levels of AASI than NDKD patients (0.55 +/- 0.14 vs. 0.45 +/- 0.16, P < 0.05). The 24-h systolic and daytime systolic BP variability of DKD patients was also higher than NDKD patients. In DKD patients, the correlation analysis revealed that the AASI showed association with 24-h systolic BP variability (24 hSBPV), 24-h diastolic BP variability (24 hDBPV),daytime diastolic BP variability (dDBPV), nighttime systolic BP variability (nSBPV) and nighttime diastolic BP variability (nDBPV), and nDBPV and age showed strong associations with AASI. CONCLUSION: Although both DKD and NDKD patients suffered from arterial stiffness, greater AASI and short-term BPV was detected in DKD patients. AASI is associated with nDBPV and age. Optimal short-term BPV control in hypertensive type 2 diabetic patients with overt nephropathy may improve arterial elasticity.

Charlson comorbidity index helps predict the risk of mortality for patients with type 2 diabetic nephropathy.

Our intent is to examine the predictive role of Charlson comorbidity index (CCI) on mortality of patients with type 2 diabetic nephropathy (DN). Based on the CCI score, the severity of comorbidity was categorized into three grades: mild, with CCI scores of 1-2; moderate, with CCI scores of 3-4; and severe, with CCI scores ≥5. Factors influencing mortality and differences between groups stratified by CCI were determined by logistical regression analysis and one-way analysis of variance (ANOVA). The impact of CCI on mortality was assessed by the Kaplan-Meier analysis. A total of 533 patients with type 2 DN were enrolled in this study, all of them had comorbidity (CCI score >1), and 44.7% (238/533) died. The mortality increased with CCI scores: 21.0% (50/238) patients with CCI scores of 1-2, 56.7% (135/238) patients with CCI scores of 3-4, and 22.3% (53/238) patients with CCI scores ≥5. Logistical regression analysis showed that CCI scores, hemoglobin, and serum albumin were the potential predictors of mortality (P<0.05). One-way ANOVA analysis showed that DN patients with higher CCI scores had lower levels of hemoglobulin, higher levels of serum creatinine, and higher mortality rates than those with lower CCI scores. The Kaplan-Meier curves showed that survival time decreased when the CCI scores and mortality rates went up. In conclusion, CCI provides a simple, readily applicable, and valid method for classifying comorbidities and predicting the mortality of type 2 DN. An increased awareness of the potential comorbidities in type 2 DN patients may provide insights into this complicated disease and improve the outcomes by identifying and treating patients earlier and more effectively.

Influence of HbA1c on short-term blood pressure variability in type 2 diabetic patients with diabetic nephropathy.

The aim of this study was to understand the characteristics of blood pressure (BP) variability in subjects with diabetic nephropathy (DN), and identify the probable predictors affecting BP variability. Fifty-one chronic kidney disease (CKD)-hypertensive patients without diabetes (NDN group) and sixty type 2 diabetic patients with overt DN (DN group) were enrolled in this study. The values of short-term BP variability were obtained from 24 h ambulatory BP monitoring (ABPM). Variance analysis or nonparametric analysis revealed that 24-h systolic BP variability and nighttime systolic BP variability of the DN group were significantly higher than those of the NDN group [(12.23±3.66) vs. (10.74±3.83) mmHg, P<0.05; (11.23±4.82) vs. (9.48±3.69) mmHg, P<0.05]. Then the patients of the DN group were divided into two groups according to glycated hemoglobin (HbA1c) level: Group A (HbA1c<7%) and Group B (HbA1c≥7%), and the t-test showed that patients in Group B had larger 24-h diastolic, daytime diastolic, and nighttime systolic/diastolic BP variability compared with Group A. In the DN group, partial correlation analysis revealed that HbA1c exhibited a strong association with 24-h diastolic, daytime diastolic, nighttime systolic and diastolic BP variability (P<0.001, P<0.001, P<0.05, and P<0.001, respectively). Taken together, larger short-term BP variability was detected in hypertensive type 2 diabetic patients with overt nephropathy and renal insufficiency. It may imply that the optimal BP variability level could benefit from a better glycaemic control.

[Vitamin D deficiency and carotid artery intima-media thickness and coronary calcification in patients with diabetic nephropathy].

OBJECTIVE: To investigate the deficiencey and insufficiency of 25-hydroxyvitamin D3 [25 (OH) D3], 1,25- dihydroxyvitamin D3 [1,25 (OH)2 D3] in patients with diabetic nephropathy (DN), an their association with carotid artery intima-media thickness (IMT) and coronary artery calicfication. METHODS: The concentrations of 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH) were determined by radioimmunoassay in 151 DN patients. Based on the level of 25-hydroxyvitamin D3, the patients were divided into Vitamin D deficiency group (Vit-D-D group, <15 ng/mL), insufficiency group (Vit-D-I group, 15-30 ng/mL), and normal group (Vit-D-N group, >30 ng/mL). The association of Vitamin D with IMT and coronary artery calcification was examined through group comparisons, logistic regression analysis and multiple linear regression analysis. RESULTS: The mean level of 25-hydroxyvitamin D3 was (28 +/- 18.1) ng/mL, with an interquartile range of 16.92 - 35.45 ng/mL. The incidence of 25-hydroxyvitamin D3 insufficiency and deficiency was 47.01% (71/151) and 18.574% (28/151) respectively. The mean level of 1,25-dihydroxyvitamin D3 was (28.93 +/- 33.13) pg/mL, with an interquartile rang of 10.36 - 31.08 pg/mL. The incidence of 1,25-dihydroxyvitamin D3 insufficiency was 77.5% (117/151). Compared with the normal controls, the BMI, 24 h urine protein, CHO and LDL of those with Vitamin D deficiency increased significantly (P < 0.05). IMT ws associated with age, sex, and serum phosphorous. Coronary clcification was negative correlated with 1,25-dihydroxyvitamin D3. CONCLUSION: The incidence of vitamin D deficiency and insufficiency in DN patients is high. The patients with vitamin D deficiency have higher urinary protein, CHO and LDL. Corornary artery calcification is reversely correlated with 1,25(OH)2D3.

[The correlation of serum cystatin C level with the severity of carotid atherosclerosis in patients with type 2 diabetes mellitus].

OBJECTIVE: To investigate whether serum cystatin C (Cys C) concentration correlates with the severity of carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (DM). METHODS: This study enrolled 633 type 2 DM patients met the inclusion/exclusion criteria. All the patients were subjected to the measurement of serum Cys C, concentration, complete blood count, and blood biochemical test. The severity of CAS was evaluated by Doppler ultrasound to define intimal medial thickness (IMT) of carotid artery, the location and size of atherosclerotic plaque. Based on the estimated glomerular filtation rate (eGFR), the patients were divided into DM with chronic kidney diease (CKD) group (DM-CKD) and DM without CKD group (DM-NCKD), then were further divided into two subgroups by IMT and AS plaque. The relationship of serum Cys C with the severity of CAS was evaluated by the comparison between the two groups, correlation analysis and multiple linear regression analysis. RESULTS: In 396 DM-NCKD patients with the eGFR > or = 60 mL/(min x 1.73 m2), Cys C concentration of IMT thickening group was higher than that of normal IMT group [(1.00 +/- 0.20) mg/L vs. (0.90 +/- 0.30) mg/L, P<0.05], but the difference was not statistically significant after the adjustment for confounding factors. The patients with obvious CAS plaques formation had higher Cys C concentration than those without AS plaques formation [(1.05 +/- 0.27) mg/L vs. (0.89 +/- 0.22) mg/L, P<0.05]. Moreover, the concentration of Cys C was correlated with the severity of CAS (r=0.338, P<0.001), even after the adjustment for confounding factors (r=0.14, P=0.005). Multiple linear regression analysis also showed a close correlation of Cys C with the severity of CAS (B= 0.071, P=0.001). Analysis of variance showed that the severity of CAS was increased accordingly with the increasing level of Cys C. However, the concentration of Cys C was not correlated with the severity of CAS in 237 DM-CKD patients. CONCLUSION: The concentration of Cys C was positively correlated with the severity of CAS, it may be a candidate marker of CAS severity in type 2 DM patients without CKD.

Noninvasive evaluation of renal oxygenation in diabetic nephropathy by BOLD-MRI.

PURPOSE: To evaluate the renal oxygenation in type 2 diabetes by blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI). MATERIALS AND METHODS: Forty-eight patients with type 2 diabetes and 67 healthy controls were recruited. All patients were further divided into four subgroups based on renal functional level. Bilateral renal cortical R2* (CR2*) and medullary R2* (MR2*) values were extracted and quantified on BOLD-MRI, then R2* ratio between medulla and cortex (MCR) was calculated. CR2*, MR2* and MCR were compared among the groups separately. The relationships were analyzed between R2* values and clinical index of renal function. RESULTS: Compared with controls, MR2* and CR2* in diabetes were significantly increased. The positive relationship was found between MR2* and estimated glomerular filtration rate (eGFR), and CR2* was negatively correlated with eGFR. Interestingly, the MCR increased in early stage of diabetes and decreased along with the aggravation of diabetic nephropathy (DN). CONCLUSION: BOLD-MRI can non-invasively detect and assess the renal hypoxia in diabetes. Our findings suggest that hypoxia in medulla is more apparent and earlier than in cortex. During the progression of DN, a reversion of corticomedullary oxygenation gradient can be detected, thus, MCR would be adopted to suppose the progression and prognosis of DN.

Effect of anaphylatoxin C3a, C5a on the tubular epithelial-myofibroblast transdifferentiation in vitro.

BACKGROUND: Tubulointerstitial renal fibrosis is the common end point of progressive kidney diseases, and tubular epithelial-myofibroblast transdifferentiation (TEMT) plays a key role in the progress of tubulointerstitial renal fibrosis. Anaphylatoxin C3a and C5a are identified as novel profibrotic factors in renal disease and as potential new therapeutic targets. The aim of this study was to investigate whether C3a, C5a can regulate TEMT by transforming growth factor-ß1 (TGF-ß)/connective tissue growth factor (CTGF) signaling pathway and the effects of C3a and C5a receptor antagonists (C3aRA and C5aRA) on C3a- and C5a-induced TEMT. METHODS: HK-2 cells were divided into C3a and C5a groups which were subdivided into four subgroups: control group, 10 ng/ml TGF-ß1 group, 50 nmol/L C3a group, 50 nmol/L C3a plus 1 µmol/L C3aRA group; control group, 10 ng/ml TGF-ß1 group, 50 nmol/L C5a group, 50 nmol/L C5a plus 2.5 µmol/L C5aRA group. TGF-ß1 receptor antagonist (TGF-ß1RA) 10 µg/ml was used to investigate the mechanism of C3a- and C5a-induced TEMT. Electron microscopy was used to observe the morphological changes. Immunocytochemistry staining, real-time PCR and Western blotting were used to detect the expressions of a smooth muscle actin (α-SMA), E-cadherin, Col-I, C3a receptor (C3aR), C5aR, CTGF and TGF-ß1. RESULTS: HK-2 cells cultured with C3a and C5a for 72 hours exhibited strong staining of α-SMA, lost the positive staining of E-cadherin, and showed a slightly spindle-like shape and loss of microvilli on the cell surface. The expressions of α-SMA, E-cadherin, Col-I, C3aR, C5aR, TGF-ß1 and CTGF in C3a- and C5a-treated groups were higher than normal control group (P < 0.05). C3aRA and C5aRA inhibited the expressions of α-SMA, Col-I, C3aR, C5aR, and up-regulated the expression of E-cadherin (P < 0.05). TGF-ß1 and CTGF mRNA expressions induced by C3a and C5a were partly blocked by TGF-ß1RA (P < 0.05). CONCLUSION: C3a and C5a can induce TEMT via the up-regulations of C3aR and C5aR mRNA and the activation of TGF-ß1/CTGF signaling pathway in vitro.