Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin.

BACKGROUND: Type-2 diabetes and diabetic kidney disease have additive effects on cardiovascular risk. Furthermore, the degree of proteinuria is an independent predictor of mortality in this patient group. We hypothesized that altered kidney clearance and/or metabolism of vasoactive peptides occurring during proteinuria could link early diabetic nephropathy to cardio vascular disease (CVD). METHODS: We performed a cross-sectional study of 85 incident patients (51 +/- 5 years, 49 males) with type-2 diabetes and 38 age- and sex-matched controls. We further divided patients by the presence of minor (<500 mg/day; n = 40) or severe (>/=500 mg/day; n = 45) proteinuria. Clinical and anthropometric data, along with ultrasonographic flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thicknesses (CIMT), were recorded in each group. Circulating NAMPT/visfatin, adiponectin (normalized to BMI), AHSG/fetuin-A and hsCRP levels were also measured using commercial ELISA. RESULTS: Plasma NAMPT/visfatin, CIMT, HOMA index and hsCRP levels were all significantly higher in diabetics than in control subjects, and all but CIMT correlated with proteinuria (rho = 0.46; P < 0.001, rho = 0.54; P > 0.05, rho = 0.32; P = 0.003, rho = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria (rho = -0.54; P < 0.001, rho = -0.56; P < 0.001, rho = -0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r(2) = -0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r(2) = -0.33, P = 0.006) were independently related to FMD. CONCLUSIONS: The present study suggests that the presence of proteinuria, regardless of the degree of renal function impairment, is an important predictor of endothelial dysfunction in early diabetic nephropathy and that it is associated with altered circulating levels of NAMPT/visfatin and adiponectin.     

Normalization of endothelial dysfunction following renal transplantation is accompanied by a reduction of circulating visfatin/NAMPT. A novel marker of endothelial damage?

Abstract:  Endothelial dysfunction is strongly linked to cardiovascular disease and outcome of patients with chronic kidney disease. We hypothesized that decreased inflammatory activity and increased adiponectin following transplantation could be one mechanism for a better endothelial health. Fifty-eight living donor kidney transplant non-diabetic recipients, 31 (23 male, 29 ± 5 yr) on cyclosporine A and 27 (10 male, 26 ± 5 yr) on tacrolimus immunsupression, were studied longitudinally. Visfatin, adiponectin, high sensitive C-reactive protein (hsCRP) levels, brachial artery flow mediated dilatation (FMD) and nitroglycerine mediated dilatation were measured before transplantation and on the 30th and 90th day after transplantation. Pre-transplantation visfatin, adiponectin and FMD values of patients were significantly higher than those of the controls (p < 0.001 for all). All values decreased significantly 30 and 90 d post-transplantation. Plasma visfatin and adiponectin, correlated negatively with FMD levels 90 d both before and after kidney transplantation (p < 0.001 for both). Endothelial function improved during the first month after transplantation, and the degree of improvement correlated to reductions in circulating visfatin, adiponectin and hsCRP levels. Of interest, the intracellular enzyme visfatin was the strongest predictor of FMD both before and after kidney transplantation and may thus reflect endothelial cell damage directly.     

Effect of renin–angiotensin–aldosterone system (RAAS) blockade on visfatin levels in diabetic nephropathy

Aim: Plasma visfatin levels are elevated in diabetic nephropathy in parallel to the severity of proteinuria and glomerular filtration rate. The aim of this study was to find out whether the renin–angiotensin–aldosterone system (RAAS) blockage has any effect on the plasma visfatin levels. Methods: Thirty‐two patients with diabetic proteinuria (>500 mg/day) with a normal glomerular filtration rate (GFR) and 33 healthy subjects were enrolled. Patients were treated with ramipril 5 mg daily for 2 months. Proteinuria, GFR, high‐sensitivity C‐reactive protein (hsCRP), visfatin, flow‐mediated dilatation (FMD) and homeostasis model assessment of insulin resistance (HOMA‐IR) index measurements were performed both before and after the treatment. Results: The plasma visfatin, and hsCRP levels of the patients were significantly higher and the FMD was significantly lower (P < 0.001 for all). The visfatin levels were significantly correlated to FMD, systolic and diastolic blood pressures, proteinuria, eGFR, HOMA‐IR and hsCRP. Ramipril treatment resulted in a significant decrease in plasma visfatin, proteinuria, hsCRP, HOMA‐IR and increase in FMD (P < 0.001) in patients (P < 0.001 for all). Conclusion: The present study suggests that plasma visfatin levels are related to the endothelial functions, inflammation and the severity of proteinuria in diabetic nephropathy. Treatment with ramipril causes a significant decrease in visfatin levels along with the improvement of proteinuria, endothelial dysfunction and inflammatory state in diabetic nephropathy.     

甲状腺素片补充治疗对慢性肾脏疾病患者甲状腺激素水平的影响研究

目的 探讨小剂量甲状腺素补充治疗对慢性肾脏疾病患者的甲状腺激素水平、营养不良及左心功能的影响.方法 湖南省人民医院2013年2月至2015年2月间收治的慢性肾脏疾病患者210例,A组为eGFR＜ 15mL ·(min·1.73m2)-1的患者(n=70),B组为15＜ eGFR＜30mL·(min·1.73m2)-1的患者(n=70),C组为30 ＜eGFR ＜60mL·(min·1.73m2)-1的未透析患者(n=70).选择同期本院体检的正常人群为正常对照组(D组,n =70).收集4组患者血液、生化临床资料,检测游离三碘甲状腺原氨酸(free triiodothyronine,FT3)、游离甲状腺素(freethyroxine,FT4)、促甲状腺激素(thyroid stimulating hormone,TSH)、C反应蛋白(C reactive protein,CRP)、左心室射血分数(left ventricular ejection fraction,LVEF)及左心室质量指数(Left ventricular mass index,LVMI),并计算主观综合性营养评估法(subjective global assessment of nutritional act,SGA)等指标.每组根据甲状腺激素水平分为正常组Ⅰ、异常组Ⅱ,观察各组间各指标差异,再给予异常组小剂量甲状腺激素干预后观察各项指标改变.结果 A、B、C组FT3均显著低于D组(P＜0.05),低T3综合征的发生率随eGFR下降而升高;正常组Ⅰ与异常组Ⅱ相比,ALB、CRP、SGA、LVEF、LVMI比较有显著差异(P＜0.05);异常组的FT3与eGFR、SGA、ALB、LVEF呈显著正相关(r=0.912,P＜0.001;r =0.721,P＜0.001;r =0.810,P＜0.001;r=0.903,P＜0.001);FT3与CRP、LVMI呈负相关(r=-0.981,P＜0.001;r=-0.442,P＜0.001);异常亚组给予小剂量甲状腺素治疗后FT3及LVEF较治疗前明显改善(P＜0.05),治疗后eGFR水平只有C2组患者有提高(P＜0.05).结论 甲状腺素水平下降与肾功能严重程度相关,以血清FT3水平降低为主;低水平FT3与营养、左心功能有显著相关性;予以小剂量的甲状腺激素治疗后的低T3及亚临床甲减者的左心收缩功能有提高,中度肾功能损伤的患者eGFR有提高.     

老年慢性肾脏病患者生活质量评估及其危险因素分析

目的:了解65岁以上慢性肾脏病（chronic kidney disease,CKD）患者的老年综合评估评分情况,并分析患者生活质量的相关影响因素。方法:本研究为回顾性队列研究,入选2016年10月至2019年10月在山西省人民医院肾内科诊断为CKD且65岁以上的189例患者,依据患者是否透析分为透析组（ ...     

Effect of urate-lowering therapy on renal function in chronic kidney disease stages 2-5

Objective To investigate the effect of urate-lowering therapy on renal function in chronic kidney disease (CKD) stages 2-5 patients with hyperuricemia (HUA). Methods A total of 132 patients of CKD stages 2-5 with HUA between July 2016 and December 2017 in Department of Nephrology of the Second Affiliated Hospital of Anhui Medical University were prospectively and self-controlled analyzed. Serum uric acid (SUA), estimated glomerular filtration rate (eGFR) and other clinical parameters were measured at baseline and after 1-6 months treatment. The patients were divided into group A (CKD stages 2-3a) and group B (CKD stages 3b-5) on the baseline value of eGFR. The changes of SUA and eGFR before and after treatment were compared. According to the level of SUA after 6 months treatment, patients were divided into attainment group (SUA＜360 μmol/L) and nonattainment group (SUA≥360 μmol/L). The difference of renal function in pre-treatment and post-treatment was compared. Multiple stepwise linear regression was used to analyze the relationship among the change of eGFR after receiving 6 months' treatment (deGFR) and SUA level, baseline eGFR and other indexes. Results After 1, 3, 6 months treatment, the average levels of SUA, Scr and urea nitrogen of all patients were decreased significantly while eGFR value was increased significantly (all P＜0.050) than those in pre-treatment period. After six-month-therapy, proteinuria and hematuria were improved significantly in all patients (P＜0.001, P=0.001). Compared with pre-treatment period, both the SUA levels of group A and group B were declined significantly while eGFR had a significant rise after treatment (P＜0.001). The change of eGFR post-treatment in group A was significantly higher than that of group B [(13.64±15.35) vs (8.97±9.79) ml?min-1?(1.73 m2)-1, P=0.044]. At 6 months after treatment, the eGFR value increased markedly in both attainment group and nonattainment group compared with pre-treatment period (P＜0.001). After six-month-therapy, the eGFR value in attainment group was increased more obviously than that of nonattainment group [(13.96±14.64) vs (8.03±9.69) ml?min-1?(1.73 m2)-1, P=0.021]. Multiple stepwise linear regression analysis showed that the baseline eGFR value was an influencing factor of deGFR (b=0.161, P=0.020). Conclusions The renal function of CKD stages 2-5 patients with HUA can be significantly improved by urate-lowering therapy, which can effectively reduce proteinuria and hematuria.     

Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function.

BACKGROUND: Adiponectin, a newly discovered collagen-like protein of the collectin family exclusively produced by adipocytes, possesses anti-inflammatory properties. Plasma adiponectin is associated with a decreased cardiovascular risk in non-renal patients, and is reduced in obesity and insulin-resistant states. Although reports show an increase in the adiponectin level in maintenance haemodialysis, peritoneal dialysis and end-stage renal disease, there is no documentation of adiponectin levels and regulation in the early stages of chronic kidney disease (CKD). METHODS: We prospectively measured glomerular filtration rate (GFR) in 48 patients with CKD using inulin clearance. Fasting blood was drawn to determine insulin, leptin, adiponectin and C-reactive protein (CRP) levels. Body fat mass was calculated using skinfold thickness measurements. RESULTS: The patients' mean GFR was 53.5+/-24.9 (SD) ml/min/1.73 m2. Adiponectin was in the normal range in men (9.8+/-2.9 mg/l) and women (16.6+/-5.0 mg/l) with CKD, being significantly higher in women than men (P<0.001). Serum leptin was above normal (10.4+/-10.7 microg/l), whereas serum insulin and CRP were within their normal ranges (3.5+/-3.3 microU/ml and 2.6+/-5.0 mg/l, respectively). In linear regression analysis, adiponectin was negatively correlated with GFR (P = 0.02), fat mass (P = 0.03) and body mass index (P = 0.002), and strongly positively correlated with serum leptin (P = 0.003). A positive relationship was also found between plasma adiponectin and the urinary albumin/creatinine ratio (P = 0.007). No relationship was found between adiponectin and insulin or adiponectin and CRP. In multiple regression analysis, adiponectin was significantly positively correlated with leptin (P<0.0001), negatively with body mass index (P<0.0001) and only weakly with GFR (P = 0.04). CONCLUSIONS: Despite an adverse metabolic environment in chronic renal insufficiency, serum adiponectin increases in non-obese patients when renal function deteriorates. Adiponectin is only weakly affected by renal function per se, but appears influenced by proteinuria, and more significantly by body mass index and the change in serum leptin that accompanies decline in renal function.     

Endothelial dysfunction and fetuin A levels before and after kidney transplantation

BACKGROUND: Endothelial dysfunction (ED) has a major role in the cardiovascular outcome of patients with chronic kidney disease (CKD). The aim of this study was to investigate the relation between fetuin A levels and ED in kidney transplant recipients. METHODS: Forty-two living donor kidney transplant recipients, 21 (11 male) on cyclosporine A and 21 (10 male) on tacrolimus-based regimes, were studied. Forty-two (21 male) healthy subjects were enrolled as controls. Fetuin A, highly sensitive C-reactive protein (hsCRP) levels, brachial artery endothelium-dependent vasodilatation (FMD), nitroglycerine mediated dilatation (NMD), and carotid intima-media thickness (CIMT) were measured before transplantation and on the 30th and 90th days posttransplant. RESULTS: Pretransplantation serum fetuin A concentrations and FMD values of patients were significantly lower than those of the controls (P<0.001 for both). These were significantly increased in the 30th and 90th days posttransplantation There was a significant positive correlation between Fetuin A and FMD levels both before and after kidney transplantation (r=0.534, r=0.576; respectively, P<0.001 for both). Carotid intima-media thickness and hsCRP levels decreased after transplantation (P<0.001 for all). According to the regression analysis, fetuin A, intact parathyroid hormone, and hsCRP levels were the independent determinants of FMD. CONCLUSION: The results of the present study suggest that low serum fetuin A levels in CKD may contribute to impaired endothelial functions in CKD. Future studies should clarify the role of fetuin A levels in cardiovascular outcomes of CKD.     

Regulation of fibroblast growth factor-23 in chronic kidney disease.

BACKGROUND: Fibroblast growth factor-23 (FGF23) is a circulating factor that regulates the renal reabsorption of inorganic phosphate (Pi) and is increased in chronic kidney disease (CKD). The aim of the current investigation was to study the regulation of FGF23 in CKD subjects with various degree of renal function. As such, we analysed the relationship between FGF23, Pi, calcium, parathyriod hormone (PTH), 25(OH) vitamin D3(25(OH)D3), 1,25(OH)2 vitamin D3(1,25(OH)2D3) and estimated glomerular filtration rate (eGFR). METHODS: Intact FGF23 and other biochemical variables were analysed in 72 consecutive adult out-patients with various stages of CKD (eGFR ranging from 4-96 ml/min.) Association studies were performed using linear univariate and multivariate analysis. RESULTS: FGF23 was significantly elevated at CKD stage 4 (266 +/- 315 pg/ml, P < 0.001) and 5 (702 +/- 489 pg/ml, P < 0.001) compared with CKD 1-2 (46 +/- 43 pg/ml). In CKD 4-5 an independent association between log FGF23 and Pi (P < 0.001), 25(OH)D3 (P < 0.05) as well as eGFR (P < 0.01) was observed. In contrast, in CKD 1-3 log PTH (P < 0.05) was the only independent predictor of log FGF23 in multivariate analysis. In CKD 1-5, Pi (P < 0.00001) and log PTH (P < 0.01) were explanatory variables for log FGF23 in multivariate analysis. CONCLUSIONS: We conclude that serum FGF23 increases in CKD 4-5, in parallel with the emerging hyperphosphataemia. Serum Pi is the most important predictor of FGF23 when GFR is less than 30 ml/min. In contrast, our data suggest that Pi may not be an important determinant of FGF23 in normophosphataemic CKD subjects. Finally, the association between FGF23 and PTH in CKD may suggest a co-regulation that remains to be further elucidated.     

Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction

We evaluated the effect of a chronic treatment with Tadalafil on progenitor cells (PCs) number and endothelial function in patients with erectile dysfunction (ED) with or without cardiovascular risk factors. Twenty-six subjects with ED and 23 aged matched controls were studied. All subjects underwent blood tests, International Index of Erectile Function (IIEF-5), Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), brachial artery flow-mediated dilation (FMD) and PCs count. International index of erectile function, FMD and PC count were re-evaluated in all subjects at the end of Tadalafil and placebo treatment. With respect to controls patients had lower basal FMD (P < 0.05) and basal PCs (P < 0.05). Treatment with Tadalafil determined a significant increase in PCs (P < 0.001) and FMD (P < 0.001) with respect to basal level. Positive correlation was found between basal FMD and PCs (P < 0.05) and between basal FMD and PCs increase after Tadalafil treatment (P < 0.05). Tadalafil promotes a mobilization of PCs and improves endothelial function in ED patients.     

尿sCD146与慢性肾脏病的关系及其临床意义的探讨

目的:探讨尿sCD146水平在慢性肾脏病(CKD)中的意义及其与肾功能相关指标的关系。方法:入选105例CKD患者,CKD1期28例,CKD2期27例,CKD3期16例,CKD4期14例,CKD5期20例,(非透析患者)。设健康对照组20例。采用ELISA法检测尿sCD146水平。分析尿sCD146在CKD各期中的变化及其与肾功能相关指标的关系。结果:CKD1～5期患者尿sCD146水平均较对照组升高。各组CKD患者尿sCD146水平[CKD1(139.53±7.69)ng/ml,CKD2(156.02±15.37)ng/ml,CKD3(174.87±2.55)ng/ml,CKD4(190.66±8.01)ng/ml,CKD5(211.76±22.99)ng/ml],均显著高于对照组(128.09±4.05)ng/ml。尿sCD146水平随着CKD1～5期进展升高,P<0.05。CKD3～5期患者超敏C-反应蛋白(hs-CRP)较对照组升高、且随着CKD的进展进行性升高(P<0.05)。相关分析显示尿sCD146与血sCD146、Scr、BUN、β2-MG、CysC、hs-CRP水平呈正相关(r分别为:0.697,0.699,0.871,0.755,0.524、0.414),与eGFR、Hb、Alb呈负相关(r分别为:-0.787,-0.601,-0.298)。结论:尿sCD146与肾功能水平密切相关,可能反映早期肾功能的损伤及严重程度,并与CKD患者机体的炎症状态相关。外周血、尿液中有sCD146的异常表达,可能参与了肾脏损伤的免疫机制,能否作为检测CKD患者早期肾功能损伤新的敏感性标志物,仍需要更多样本的临床研究证实。     

Levels of bisphenols in patients with chronic kidney disease and their correlation with renal function

Objective To observe the levels of four bisphenols (bisphenol A, B, S and F) and their correlation with renal function in chronic kidney disease (CKD) patients. Methods Patients with CKD were identified according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Sixty-three CKD patients and eleven healthy controls were enrolled. CKD patients were further classified as mild renal injury group (CKD stage 1 and 2, n=30), moderate renal injury group (CKD stage 3, n=19) and severe renal injury group (CKD stage 4 and 5, n=14). The levels of four bisphenols in serum were determined by high performance liquid chromatography (HPLC). The correlation between concentrations of four bisphenols and estimated glomerular filtration rate (eGFR) was assessed by Spearman's rank correlation analysis. The associations of four bisphenols with coronary heart disease, diabetes and hypertension in CKD patients were estimated by binary multivariate logistic regression. Results (1) Four bisphenols were not detected in serum of healthy control. In the mild renal injury group the bisphenol A and bisphenol S were not detected, and patients had 5.24 (5.24, 9.38) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In the moderate renal injury group bisphenol S was not detected, and patients had 2.79 (1.01, 4.53) μg/L bisphenol A, 5.24 (5.24, 5.24) μg/L bisphenol B and 0.74 (0.74, 0.74) μg/L bisphenol F. In severe renal injury group patients had 14.30 (7.97, 18.17) μg/L bisphenol A, 0 μg/L bisphenol B, 23.73 (23.73, 136.59) μg/L bisphenol S and 0.74 (0.74, 1.42) μg/L bisphenol F. The levels of bisphenol A and bisphenol S in severe renal injury group were higher than those in the healthy control group, mild renal injury group and moderate renal injury group (all P＜0.05). Bisphenol B and bisphenol F were not statistically different among four groups. (2) Bisphenol A and bisphenol S were negatively correlated with eGFR (r=-0.779, P＜0.001; r=-0.546, P＜0.001). (3) Among CKD patients, bisphenol A was correlated with diabetes (OR=4.951, 95%CI 1.603-15.294, P=0.005), and bisphenol S was correlated with hypertension (OR=4.466, 95%CI 1.575-12.666, P=0.005). Conclusions CKD patients have a variety of bisphenol compounds, especially bisphenol A and bisphenol S. Bisphenol A and bisphenol S have high levels, and their exposures are correlated with renal function.     

Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome

AIM: Plasma adiponectin levels are well associated with metabolic syndrome. However, the relationship between hypertension and plasma adiponectin levels is not clear. Also, there is not enough data about the effects of different antihypertensive regimens on plasma adiponectin levels. METHODS: Ninety-six hypertensive patients (48 male, 48 female) who fulfil the diagnostic criteria of metabolic syndrome were enrolled. Patients were treated for 3 months with metoprolol (n = 18, 100 mg/day), amlodipine (n = 20, 10 mg/day), doxazosin (n = 18, 4 mg/day), ramipril (n = 20, 5 mg/day) and valsartan (n = 20, 80 mg/day). Blood biochemistry and plasma adiponectin concentrations were measured both before and after the study. Insulin resistance was measured by homeostasis assessment index (HOMA). RESULTS: Plasma adiponectin levels were correlated with the total cholesterol (r = -0.244, P = 0.017), triglyceride (r = -0.306, P = 0.002), high-density lipoprotein-cholesterol (r = 0.286, P = 0.005), body mass index (r = -374, P < 0.001), systolic (r = -502, P < 0.001) and diastolic blood pressures (r = -235, P = 0.021). The independent predictors of plasma adiponectin levels were HOMA (beta = -0.199, P = 0.02), body mass index (beta = -0.313, P < 0.001) and systolic blood pressures (beta = -0.483, P < 0.001). Ramipril and valsartan increased the plasma adiponectin levels significantly higher than the other regimens (P < 0.05 for both) while metoprolol did not make a significant effect. CONCLUSION: According to the results, plasma adiponectin levels are associated with the arterial blood pressures, body fat content and the lipid parameters in hypertensive patients with metabolic syndrome. The effects of antihypertensive drugs on plasma adiponectin levels are parallel to their effects on blood pressures and insulin sensitivities. The different effects of several regimens on plasma adiponectin levels and insulin sensitivities may account for the diversity of the cardiovascular outcomes in patients with hypertension.     

Effects of lipid-lowering treatment on platelet reactivity and platelet-leukocyte aggregation in diabetic patients without and with chronic kidney disease: a randomized trial

Background Diabetes mellitus (DM) is associated with hyperreactive platelets and increased platelet-leukocyte aggregation (PLA), but the impact of concomitant chronic kidney disease (CKD) has been much less studied. Lipid-lowering treatment (LLT) may have favorable effects on platelet activation and inflammation. The objective of this mechanistic study was to investigate the impact of CKD on platelet function and inflammatory parameters in patients with DM and the effects of LLT. Methods After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S + E) were compared in a randomized, double-blind, cross-over study on platelet reactivity, PLA formation and inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1.73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75 mL/min (DM-only) were included. Results PLAs were elevated at baseline in DM-CKD compared with DM-only (P = 0.04). S + E reduced PLAs among total leukocytes and neutrophils in DM-CKD patients (P = 0.01 for both) but not in the DM-only group. Platelet reactivity did not differ between patient groups or with LLT. Plasma levels of sCD40L (P < 0.001), elastase (P < 0.01) and von Willebrand factor (VWF) (P < 0.001) were elevated in DM-CKD compared with DM-only. S + E reduced sCD40L in DM-CKD patients (P = 0.01), but LLT did not influence VWF or elastase. Conclusions DM patients with CKD stages 3-4 had increased PLA and inflammatory activity compared with DM patients with normal GFR. Simvastatin + ezetimbe decreased PLAs and plasma sCD40L in DM patients with concomitant CKD. Clinical Trial registration http://www.clinicaltrials.gov. Identifier NCT01035320.     

Implication of CKD-EPI Equation to Estimate Glomerular Filtration Rate in Chinese Patients with Chronic Kidney Disease

Abstract

Objective: To evaluate the applicability of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in Chinese patients of different stages of CKD. Methods: The CKD-EPI equation estimated GFR (eGFR) was compared with body surface area standardized GFR (sGFR), which was measured by diethylenetriaminepentaacetic acid renal dynamic imaging method in 142 CKD cases. Results: eGFR was positively correlated with sGFR (r = 0.838, p < 0.001). eGFR of 15%, 30%, and 50% accuracy were 31.0%, 57.7%, and 76.8%, respectively. Average deviation of eGFR from sGFR was ?0.92 ± 16.36 mL/min/1.73 m² (p = 0.506). There was no significant deviation in the CKD from stages 2 to 5. However, in CKD stage 1, the deviation was increased with the value of 13.36 ± 18.44 mL/min/1.73 m² (p = 0.023). Conclusion: CKD-EPI equation might be widely used in evaluation of Chinese CKD patients of different stages, with a less deviation and higher accuracy. However, in CKD stage 1, eGFR was higher than sGFR on average. It was suggested that eGFR might be overcorrected or overestimated. These results demonstrated that careful modification of CKD-EPI equation would be necessary in Chinese populations with CKD.     

Renal ultrasound elastography can reflect clinical-pathological changes in chronic kidney disease patients

Objective To analyze how is the elastography of renal tissue correlated to clinical biochemical indexes and pathological changes in patients with chronic kidney disease (CKD), and to explore the potential of renal elastography to become a new noninvasive method available for the dynamic monitoring of renal disease progression, as well as its efficacy assessment and prognosis evaluation. Methods Patients admitted to the department of nephrology of the First Affiliated Hospital of China Medical University and received renal biopsy from August 2014 to January 2015 were selected. One hundred and thirteen cases of CKD patients, 61 males and 52 females were enrolled, including 23 cases of IgA nephropathy, 39 cases of membranous nephropathy, 15 cases of minimal change nephropathy and 7 cases of focal segmental glomerulosclerosis. The Young modulus of renal cortex and medulla (YMcortex and YMmedulla) were detected by Aix Plorer type full digital color Doppler ultrasound. The correlations between the YMs and clinical biochemical indicators in blood and urine, and the difference of YMs among different pathological changes in patients with CKD were analyzed by statistics. Results The YMcortex and YMmedulla in CKD patients were higher than those in the control group (all P＜0.05); and with the progression of CKD, the YMcortex and YMmedulla gradually increased. The YMcortex in CKD G5 patients was higher than that in CKD G1-3 patients (all P＜0.05). The YMmedulla in CKD G3-5 patients was higher than that in CKD G1-2 patients (all P＜0.05). The YMcortex was correlated with systolic pressure, serum creatinine, cystatin C, serum albumin, serum phosphorus, calcium and phosphorus product, uric acid, intact parathyroid hormone (iPTH), urinary NAG, estimate glomerular filtration rate (eGFR) and hemoglobin (all P＜0.05). The YMmedulla was correlated with systolic pressure, serum creatinine, serum albumin, uric acid, iPTH, urine microalbumin (MA), urinary NAG and hemoglobin (all P＜0.05). Serum cystatin C (β=0.485, P=0.018) and uric acid (β=0.418, P=0.039) were independently correlated with the YMcortex. Serum creatinine (β=0.380, P=0.019), uric acid (β=0.482, P=0.004) and smoking (β=0.337, P=0.009) were independently correlated with YMmedulla. The YMcortex and YMmedulla in different pathological types were statistically significant (P＜0.001, P=0.003). The YMcortex and YMmedulla in patients with membranous nephropathy and IgA nephropathy were higher than those in the patients with minimal change nephropathy (all P＜0.05). The YMmedulla in patients with focal segmental glomerulosclerosis was higher than that in the patients with minimal change nephropathy (P＜0.05). The YMcortex in the patients with phases Ⅳ and Ⅴ based on the Lee grading system of IgA nephropathy was higher than that in the patients with phases Ⅱ and Ⅲ (P＜0.05). According the Oxford classification for IgA nephropathy, the YMcortex and YMmedulla in the T1 and T2 patients were higher than those in the T0 patients (P＜0.05). The YMcortex and YMmedulla showed no statistically significant differences among different stages of membranous nephropathy. Conclusions The YMcortex and YMmedulla are associated with the progress of renal insufficiency, which may become new indicators for determining CKD progression. The renal ultrasound elastography may become a new non-invasive method for early diagnosing CKD, dynamic monitoring disease progression, and assessing efficacy and prognosis.     

Primary care-based disease management of chronic kidney disease (CKD), based on estimated glomerular filtration rate (eGFR) reporting, improves patient outcomes.

BACKGROUND: The majority of patients with chronic kidney disease (CKD) stages 3-5 are managed within primary care. We describe the effects, on patient outcomes, of the introduction of an algorithm-based, primary care disease management programme (DMP) for patients with CKD based on automated diagnosis using estimated glomerular filtration rate (eGFR) reporting. METHODS: Patients within West Lincolnshire Primary Care Trust, UK, population 223, 287 with CKD stage 4 or 5 were enrolled within the DMP between March 2005 and October 2006. We have analysed the performance against clinical targets looking at a change in renal function prior to and following joining the DMP and the proportion of patients achieving clinical targets for blood pressure control and lipid abnormalities. RESULTS: Four hundred and eighty-three patients with CKD stage 4 or 5 were enrolled in the programme. There were significant improvements in the following parameters, expressed as median values (interquartile range) after 9 months in the programme, compared to baseline and percentage values patients achieving target at 9 months: total cholesterol 4.2 (3.45-5.0) mmol/l versus 4.6 (3.9-5.4) mmol/l (P < 0.01), 75.0% versus 64.5% (P < 0.001); LDL 2.2 (1.6-2.8) mmol/l versus 2.5 (1.9-3.2) mmol/l (P < 0.01), 81.9% versus 69.2% (P < 0.05); systolic blood pressure 130 (125-145) mmHg versus 139 (124-154) mmHg (P < 0.05), 56.2% versus 37.1% (P < 0.05) and diastolic blood pressure 71 (65-79) mmHg versus 76 (69-84) mmHg (P < 0.01), 68.4% versus 90.3% (P < 0.01). The median fall (interquartile range) in eGFR in the 9 months prior to joining the programme was 3.69 (1.49-7.46) ml/min/1.73 m(2) compared to 0.32 (-2.61-3.12) ml/min/1.73 m(2) in the 12 months after enrolment (P < 0.001). One hundred and twenty-two patients experienced a fall in eGFR of > or = 5 ml/min/1.73 m(2), median 9.90 (6.55-12.36) ml/min/1.73 m(2) in the 9 months prior to joining the programme, whilst in the 12 months after enrolment, their median fall in eGFR was -1.70 (-6.41-1.64) ml/min/1.73 m(2) (P < 0.001). In the remaining patients, the median fall in eGFR was 1.92 (0.41-3.23) ml/min/1.73 m(2) prior to joining the programme and 0.86 (-1.03-3.53) ml/min/1.73 m(2) in the 12 months after enrolment (P = 0.082). CONCLUSIONS: These data suggest that chronic disease management in this form is an effective method of identifying and managing patients with CKD within the UK. The improvement in cardiovascular risk factors and reduction in the rate of decline of renal function potentially have significant health benefits for the patients and should result in cost savings for the health economy.     

Relationship between serum adiopocyte fatty acid binding protein and atherosclerosis in chronic kidney disease

Objective To investigate the expression of serum adiopocyte fatty acid binding protein(A-FABP) in chronic kidney disease (CKD) and the role that A-FABP plays in CKD with atherosclerosis. Methods A total of 138 patients with CKD and 20 health control volunteers (HC) were involved in this study. The levels of serum A-FABP, free fatty acid (FFA), interleukin- 6 (IL-6), monocyte chemotactic protein 1(MCP-1) were measured by enzyme-linked immunosorbent assay(ELISA). Inteima-media thickness of common carotid artery was measured by color doppler ultrasound.Results According to the progression of glomerular filtration rate(GFR), the patients with CKD were divided into three groups: group CKD1-2[eGFR≥ 60 ml·min-1·(1.73 m2)-1], group CKD 3-4[60 ml·min-1·(1.73 m2)-1 > eGFR ≥ 15 ml·min-1·(1.73 m2)-1], group CKD5[eGFR ＜ 15 ml·min-1·(1.73 m2)-1].The levels of serum A-FABP were relatively higher in CKD than that in HC group(P＜0.05), and that in the group CKD5 were the most highest (P＜0.01). The level of serum FFA in group CKD 1-2 was relatively higher than that in group HC (P＜0.05), and FFA had a rising trend with decreased eGFR. The level of serum A-FABP was positively correlated with the levels of serum FFA (r＝0.825, P＜0.01), and also positively correlated with IL-6 (r＝0.569, P＜0.01), MCP-1(r＝0.657, P＜0.01) in CKD by Pearson correlation analysis. The levels of A-FABP in 56 patients of CKD with vascular atherosclerosis were significantly higher than that in 82 patients without vascular atherosclerosis (P＜0.01). Conclusion Serum A-FABP maybe play an important role in the progression of vascular atherosclerosis in CKD.     

Relationship between interventricular septum thickness and renal function in patients with type 2 diabetes mellitus

Objective To investigate the relationship between interventricular septum thickness(IVS) and renal function in patients with diabetes mellitus. Methods Two hundred and sixty-five patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study. According to their IVS, the patients were divided into normal group (IVS≤11 mm) and higher IVS group (IVS＞11 mm). All patients according to evaluated glomerular filtration rate (eGFR) level were divided into eGFR≥60 ml?min-1?(1.73 m2)-1 group and eGFR＜60 ml?min-1?(1.73 m2)-1 group. The demographic characteristic, biochemical examination, eGFR, and proteinuria of different groups were compared. Pearson or spearman correlation was used to analyze the relationship between eGFR, IVS and other parameters. eGFR＜60 ml?min-1?(1.73 m2)-1 and IVS thickening were analyzed by binary logistic regression. Risk factors affect the prognosis of renal function in patients with diabetes mellitus were analyzed by Cox regression analysis. Results Compared with normal group, patients in the higher IVS group had higher systolic pressure (P=0.002), their level of Scr, BUN, 24 h urinary protein were increased (all P＜0.05), while the level of eGFR, albumin (ALB), hemoglobin (Hb) and fasting blood glucose were decreased (all P＜0.05). The prevalence of hypertension was increased (81.16% vs 58.67%, χ2=11.273, P=0.001), and there was also a difference in the proportion of patients in each stage of CKD (χ2=34.593, P＜0.001). Correlation analysis showed that IVS was positively correlated with BMI, systolic BP, Scr, BUN, 24 h urinary albumin, 24 h urinary protein (all P＜0.05), while negative correlation was observed between the thickened degree of IVS and Hb, albumin, eGFR and total calcium (all P＜0.05). It's worth noting that IVS also correlated with history of hypertension and degree of renal injury (all P＜0.01). Logistic regression analysis showed that longer duration of diabetes, higher systolic pressure and BUN were independent risk factors for eGFR＜60 ml?min-1?(1.73 m2)-1 (all P＜0.05), while higher Hb and Alb were independent protective factors for eGFR＜60 ml?min-1?(1.73 m2)-1 (all P＜0.05). Logistic regression analysis also showed that the baseline increased Scr was independent risk factor for interventricular thickening (P＜0.05), while the increase of fasting blood-glucose was independent protective factor for interventricular thickening (P＜0.05). Cox regression analysis showed that interventricular thickening was an independent risk factor in predicting the progression of type 2 diabetes (HR=1.396, 95%CI=1.098-1.774, P=0.006). Conclusion Interventricular septum thickness is closely related to the state of renal function, as well as is an independent risk factor to predict kidney function decline in patients with type 2 diabetes.     

sCD146与慢性肾脏病的关系及其临床意义的研究

目的：探讨外周血sCD146水平在慢性肾脏病（CKD）中的意义及其与肾功能其他相关指标的关系。方法：入选101例CKD患者,CKD1期28例,CKD2期25例,CKD3期16例,CKD4期14例,CKD5期18例,（无血透患者）。设健康对照组20例。采用ELISA法检测sCD146水平。分析sCD146在CKD各期中的变化及其与肾功能相关指标的关系。结果：各组CKD患者sCD146水平[CKD1（218.46±34.31）ng/ml,CKD2（245.94±21.82）ng/ml,CKD3（273.99±21.87）ng/ml,CKD4（295.55±21.79）ng/ml,CKD5（326.55±26.75）ng/ml],均显著高于对照组（196.22±30.83）ng/ml。sCD146水平随着CKD1～5期进展升高,P〈0.05。相关分析显示sCD146与Scr、BUN、β2-MG、CysC水平呈正相关（r分别为：0.676,0.680,0.685,0.604）,与eGFR、Hb呈负相关（r分别为：-0.802,-0.586）。多因素逐步回归分析显示eGFR、Scr是影响sCD146的独立因素。结论：sCD146与CKD肾脏血管内皮损伤密切相关;sCD146较好地反映了CKD患者肾功能的进展及严重程度;sCD146能在一定程度上反映肾脏内皮细胞的早期损伤情况,其能否作为检测CKD患者肾功能损伤新的内源性标志物,有待进一步研究。