Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

Background

The pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians'' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.

Methods

This study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m²/y) over follow-up of more than 3 years.

Results

Of all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.

Conclusions

Ang-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.     

Association of hsCRP,White Blood Cell Count and Ferritin with Renal Outcome in Chronic Kidney Disease Patients

Inflammation is a pathogenic factor in renal injury, but whether inflammation is related to renal outcome in chronic kidney disease (CKD) patients is little known. We thus assess the association of inflammation and renal outcome in an advanced CKD cohort. This study analyzed the association between inflammatory markers, such as C-reactive protein (hsCRP), white blood cell (WBC) count and ferritin, renal replacement therapy (RRT) and rapid renal progression (estimated GFR slope<-6 ml/min/1.73 m²/y) in 3303 patients with stage 3–5 CKD. In all subjects, the mean hsCRP, WBC count, and ferritin levels were 1.2 (0.4, 5.4) mg/L, 7.2±2.3×10³ cells/µL, and 200 (107,349) ng/mL, respectively. During a mean 3.2-year follow-up, there were 1080 (32.7%) subjects commencing RRT, and 841(25.5%) subjects presenting rapid renal progression. Both hsCRP and ferritin were associated with increased risk for RRT with the adjusted HR (tertile 3 versus tertile 1∶1.17 〔1.01–1.36〕 and 1.20 〔1.03–1.40〕, respectively). Both hsCRP and ferritin were associated with increased odds for rapid renal progression with the adjusted OR (tertile 3 versus tertile 1∶1.40 〔1.13–1.77〕 and 1.32 〔1.06–1.67〕, respectively). hsCRP and ferritin stratified by albumin were also associated with RRT and rapid renal progression. Instead, WBC count was not associated with renal outcome. In conclusion, elevated levels of hsCRP and ferritin are risk factors associated with RRT and rapid renal progression in advanced CKD patients.     

Clinicopathologic Features and Prognosis of Type 2 Diabetes Mellitus and Diabetic Nephropathy in Different Age Groups: More Attention to Younger Patients

Objective: Our study sought to investigate the clinicopathologic features and renal prognosis of patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different age groups.Methods: A total of 315 patients with T2DM and biopsy-proven DN were enrolled and divided into three groups by age: the Youth group (≤44 years old), the Middle-aged group (45 to 59 years old), and the Elderly group (≥60 years old).Results: The Youth group, Middle-aged group, and Elderly group accounted for 19.05% (60/315), 59.37% (187/315), and 21.59% (68/315) of the patients in our study, respectively. The patients in the Youth group had a higher estimated glomerular filtration rate (calculated using the Chronic Kidney Disease–Epidemiology collaboration formula) (P<.001), a higher incidence of diabetic retinopathy (P = .044), and a higher incidence of being in the lower-risk chronic kidney disease heat map category (P = .046) but lower duration of diabetes (P = .016). Histologically, patients in the Youth group had the highest incidence of glomerular classification in class I (P = .006) and arteriolar hyalinosis score of 0 (P = .005). The renal survival among the three groups was comparable (P>.05).Conclusion: This study indicated that there were different clinicopathologic features among Chinese DN patients in different age groups. Although the Youth group had a relatively lower rapid kidney disease progression rate, there were no significant differences in renal survival rate among the three groups, which calls more attention to early supervision and prevention for younger DN patients.Abbreviations: CKD = chronic kidney disease; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; G&Y&O = green and yellow and orange; IFTA = interstitial fibrosis and tubular atrophy; T2DM = type 2 diabetes mellitus     

西格列汀对早期2型糖尿病肾病患者肾功能的影响

目的:研究西格列汀对早期2型糖尿病肾病患者肾小球、肾小管标志性蛋白/酶的影响。方法:早期2型糖尿病肾病患者72例,随机数字表分为对照组36例、治疗组36例;两组均采用糖尿病饮食管理、运动治疗,在控制血糖、血脂、血压的基础上,治疗组给予磷酸西格列汀100 mg 1粒/次,1次/天,持续服药6月。观察治疗前、后两组血肌酐(Scr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、血脂、空腹血糖(FBG)、餐后2小时血糖(2 h PBG)、血清胱抑素-C(Cys-C)及24 h尿微量白蛋白(24 h UAE)、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)的变化。结果:治疗后,治疗组血脂、Hb A1c、FBG、2 h PBG较对照组明显下降,差异有显著性(P0.05)。两组患者24 h UAE、NAG、β2-MG和Cys-C较治疗前均下降,差异有显著性(P0.05);两组治疗后相比,差异具有统计学意义(P0.05)。结论:西格列汀可以有效控制早期DN患者的血糖水平,减少血清Cys-C、尿微量白蛋白水平,减轻肾小管损伤,有利于延缓DN的病程和进展。     

卡托普利与坎地沙坦对老年糖尿病肾病患者肾功能的影响

目的:研究卡托普利联合坎地沙坦对糖尿病肾病患者肾功能的影响及临床疗效。方法:选择2014年5月-2015年5月我院收治的糖尿病肾病患者90例,根据治疗方法不同分为观察组和对照组。对照组给予卡托普利治疗,观察组在对照组基础上加用坎地沙坦治疗。观察并比较两组患者的临床疗效以及治疗前后空腹血糖、血尿素氮、血肌酐、24 h尿蛋白等水平的变化情况。结果:观察组的治疗总有效率为93.3%,对照组的治疗总有效率为84.4%;观察组患者的临床疗效显著高于对照组,但差异并不具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后的空腹血糖、血尿素氮、血肌酐及24 h尿蛋白水平均显著降低,差异具有统计学意义(P0.05);治疗后,观察组患者的空腹血糖、血尿素氮、血肌酐和24 h尿蛋白值均显著均明显低于对照组,差异均具有统计学意义(P0.05)。结论:卡托普利联合坎地沙坦治疗糖尿病肾病较单独采用卡托普利治疗能够更加有效的改善患者的临床症状,保护患者的肾功能,具有较好的临床疗效。     

Serum Tryptase Monitoring in Indolent Systemic Mastocytosis: Association with Disease Features and Patient Outcome

Background

Serum baseline tryptase (sBT) is a minor diagnostic criterion for systemic mastocytosis (SM) of undetermined prognostic impact. We monitored sBT levels in indolent SM (ISM) patients and investigated its utility for predicting disease behaviour and outcome.

Methods

In total 74 adult ISM patients who were followed for ≥48 months and received no cytoreductive therapy were retrospectively studied. Patients were classified according to the pattern of evolution of sBT observed.

Results

Overall 16/74 (22%) cases had decreasing sBT levels, 48 (65%) patients showed increasing sBT levels and 10 (13%) patients showed a fluctuating pattern. Patients with significantly increasing sBT (sBT slope ≥0.15) after 48 months of follow-up showed a slightly greater rate of development of diffuse bone sclerosis (13% vs. 2%) and hepatomegaly plus splenomegaly (16% vs. 5%), as well as a significantly greater frequency of multilineage vs. mast cells (MC)-restricted KIT mutation (p = 0.01) together with a greater frequency of cases with progression of ISM to smouldering and aggressive SM (p = 0.03), and a shorter progression-free survival (p = 0.03).

Conclusions

Monitoring of sBT in ISM patients is closely associated with poor prognosis disease features as well as with disease progression, pointing out the need for a closer follow-up in ISM patients with progressively increasing sBT values.     

下肢动脉硬化闭塞症患者血清胆红素含量的分析

目的：分析血清胆红素与动脉硬化闭塞症的相关性及临床意义。方法：1）回顾性分析我院2011年1月至2012年11月,318例符合下肢动脉硬化闭塞症诊断者的血清胆红素含量。并依照Fontaine分类法将患者分成临床四期。2）回顾性分析我院体检中心2012年100例体检者的血清胆红素含量。3）将上述1、2组的数据做两样本t检验,并将1组数据根据临床的分级进行内部小组t检验。以P〈0．05为有差异,P〈0．01为有显著差异。结果：动脉硬化闭塞症的患者血清总胆红素、直接胆红素、间接胆红素的含量均明显低于正常对照组,且动脉硬化闭塞症患者随着临床分级的进展而进一步降低。结论：动脉硬化闭塞症患者的血清胆红素水平与其发生成负性相关,低浓度血清胆红素是独立的动脉硬化闭塞症的危险因素。     

红花黄色素联合贝那普利对早期糖尿病肾病患者肾功能的影响

目的:探讨红花黄色素联合贝那普利对早期糖尿病肾病患者肾功能的影响。方法:选择2014年1月至2014年8月我院收治的120例早期糖尿病肾病患者为研究对象,并根据随机数字法,将其分为对照组(贝那普利治疗)和观察组(红花黄色素联合贝那普利治疗),每组各60例患者,观察和比较治疗前后两组患者中医证候变化情况、临床疗效以及血清胱抑素C(Cys C)、同型半胱氨酸(Hcy)、血肌酐(Scr)、尿素氮(BUN)、空腹血糖(FBG)、餐后2h血糖(2h PG)、糖化血红蛋白(Hb A1C)水平的变化情况。结果:与治疗前相比,两组治疗后的中医症候总积分、FBG、2h PG、Hb A1C、Cys C、Hcy、Scr、BUN水平均明显降低(P0.05);且观察组治疗后的中医症候总积分、FBG、2h PG、Hb A1C、Cys C、Hcy、Scr、BUN水平均明显低于对照组(P0.05)。观察组治疗的总有效率明显高于对照组(P0.05)。结论:红花黄色素联合贝那普利治疗能够较好地改善早期糖尿病肾病患者的肾功能,值得临床推广。     

Renal Outcomes of Pioglitazone Compared with Acarbose in Diabetic Patients: A Randomized Controlled Study

ObjectiveTo assess the effect of pioglitazone on renal outcome, including urinary albumin excretion and estimated glomerular filtration rate (eGFR), in diabetic patients.DesignA prospective, randomized, open-labeled, controlled study.SettingTaipei Veterans General Hospital.PatientsSixty type 2 diabetic patients treated with sulfonylureas and metformin, whose glycated hemoglobin (HbA1c) levels were between 7% and 10% and eGFR was between 45 and 125 mL/min/1.73 m².InterventionThe patients were randomized to receive acarbose or pioglitazone and followed up for 6 months. Thirty patients were randomly assigned to receive acarbose, and 30 patients were assigned to receive pioglitazone.MeasurementsThe primary study endpoint was the changes in the urinary albumin-to-creatinine ratio (UACR). The secondary endpoint was the changes in eGFR and other parameters.ResultsAfter 6 months of treatment, the mean changes in UACR were −18 ± 104 and 12 ± 85 (p = 0.25, between groups) for the acarbose and pioglitazone groups, respectively. The mean changes in eGFR were 0 ± 14 and −7 ± 16 mL/min/1.73 m² (p = 0.09, between groups) for the acarbose and pioglitazone groups, respectively. The reductions in HbA1c were similar in both groups. Fasting blood glucose was lower in the pioglitazone group than in the acarbose group. Significant body weight gain was observed in the pioglitazone group as compared with the acarbose group (1.3 ± 2.8 vs. −0.6 ± 1.5 kg, p = 0.002).ConclusionIn type 2 diabetic patients who were treated with sulfonylureas and metformin and possessed HbA1c levels between 7% and 10%, additional acarbose or pioglitazone for 6 months provided similar glycemic control and eGFR and UACR changes. In the pioglitazone group, the patients exhibited significant body weight gain.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01175486","term_id":"NCT01175486"}}NCT01175486     

川芎嗪联合缬沙坦治疗糖尿病肾病肾衰竭的临床疗效观察

目的:探讨川芎嗪联合缬沙坦治疗糖尿病肾病肾衰竭的临床疗效。方法:选择我院2011年1月至2013年1月收治的糖尿病肾病肾衰竭患者96例,并将其随机分为实验组和对照组,每组48例。两组患者均根据病情给予对症支持治疗,并严格控制血糖。在常规治疗基础上,实验组患者给予川芎嗪注射液240 mg,静脉滴注,1次/d,同时给予缬沙坦80 mg,口服,1次/d,21天为1个疗程;对照组患者给予缬沙坦80 mg,口服,1次/d,21天为1个疗程。1个疗程后观察两组患者的临床疗效、血液学指标、尿检指标等实验室检查。结果:治疗21天后,实验组的临床有效率达83.3%,显著高于对照组(60.4%),差异具有统计学意义(P0.05);两组空腹血糖、尿蛋白、尿素氮、血肌酐水平均较治疗前显著改善,且实验组以上指标及胆固醇水平的改善程度明显优于对照组,差异有统计学意义(P0.05)。治疗过程中,两组均无严重不良反应发生。结论:川芎嗪联合缬沙坦可以更有效地改善糖尿病肾病肾衰竭患者的临床疗效,有一定的临床应用价值。     

自拟益肾汤对早期糖尿病肾病患者尿白蛋白的影响及部分机制探讨

目的：观察自拟益肾汤对早期糖尿病肾病尿白蛋白的临床疗效及部分作用机制。方法：将本院收治的60例2型糖尿病肾病患者根据随机方法分为对照组（30例）和观察组（30例）,2组患者均接受健康教育、合理饮食指导,内科降糖治疗,常规口服缬沙坦,80 mg／d;合并高脂血症者加服辛伐他汀,20 mg／d。观察组在上述常规治疗基础上加用自拟益肾汤,水煎药方200 mL,1剂／d（早晚分服）,连用12周,1个疗程结束后观察2组患者治疗前后24 h尿微量白蛋白定量、糖化血红蛋白（HbAlc）、空腹血糖（FGC）、餐后2 h血糖（2 h BG）的变化;以及血清中 PI3K、Akt、p-Akt、bad、p-bad、Bcl-2,Bax、Caspase-3蛋白表达水平的变化。结果：1）2组治疗后24 h尿微量白蛋白定量、FPG、OGTT均较治疗前降低,与对照组比较,观察组降低的程度较为明显（P＜0．05）;2）2组治疗后血清中PI3K、p-Akt、p-bad、Bcl-2的蛋白表达均较治疗前升高, Bax、Caspase-3蛋白表达较治疗前降低,与对照组比较,观察组改变的幅度比较明显（P＜0．05）。结论：自拟益肾汤具有明显地降低糖尿病肾病蛋白尿作用,其机制可能与PI3 K／Akt信号转导通路有关。     

Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

Background

The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population.

Objective

To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality.

Methods

Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed.

Results

GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016).

Conclusion

Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients.     

Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study

Background and Objectives

Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored.

Design and Patients

Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study.

Results

Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort.

Conclusions

This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse.     

血液透析与血液灌流对终末期糖尿病肾病患者胰岛素抵抗及血清炎症因 子水平的影响

目的:探讨血液透析联合血液灌流治疗终末期糖尿病肾病的疗效以及对患者胰岛素抵抗及血清炎症因子水平的影响。方法:选择2013年7月-2015年7月在我院接受治疗的100例终末期糖尿病肾病患者作为研究对象。根据治疗方法不同,将所选研究对象分为研究组和对照组。研究组采用血液透析联合血液灌流治疗,对照组采用血液透析联合血液透析滤过治疗。观察并比较两组患者治疗前后胰岛素抵抗程度及血清C反应蛋白(CRP),肿瘤坏死因子-α(TNF-α)及白介素-6(IL-6)水平的变化情况。结果:治疗前,两组患者FBG、FINS、Homa-IR、CRP、TNF-α及IL-6水平比较差异均无统计学意义(P0.05);与治疗前比较,两组患者治疗后FBG、FINS、Homa-IR、CRP、TNF-α及IL-6水平均显著降低,差异具有统计学意义(P0.05),且研究组患者治疗后FBG、FINS、Homa-IR、CRP、TNF-α及IL-6水平均明显低于对照组,差异具有统计学意义(P0.05)。结论:与血液透析联合血液透析滤过方法比较,血液透析联合血液灌流治疗能够更有效的改善ESDN患者胰岛素抵抗程度,降低炎症因子水平,值得临床进一步推广应用。     

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy

Objective

Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.

Methods

Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).

Results

Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).

Conclusion

These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.     

Thiazolidinediones and Risk of Long-Term Dialysis in Diabetic Patients with Advanced Chronic Kidney Disease: A Nationwide Cohort Study

Thiazolidinediones (TZDs) reduce urinary albumin excretion and proteinuria in diabetic nephropathy. The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease (CKD) is unknown. We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD. The nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance Research Database. From January 2000 to June 2009, 12350 diabetic patients with advanced CKD (serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy) were selected for the study. We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios (HRs) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users (n=1224) as compared to nonusers (n=11126). During a median follow-up of 6 months, 8270 (67.0%) patients required long-term dialysis and 2593 (21.0%) patients died before starting long-term dialysis. Using propensity score matched analysis, we found TZD users were associated with a lower risk for long-term dialysis (HR, 0.80; 95% confidence interval [CI], 0.74-0.86) and the composite outcome of long-term dialysis or death (HR, 0.85; 95% CI, 0.80-0.91). The results were consistent across most patient subgroups. Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death. Further randomized controlled studies are required to validate this association.     

Probiotic Soy Milk Consumption and Renal Function Among Type 2 Diabetic Patients with Nephropathy: a Randomized Controlled Clinical Trial

Probiotics and Antimicrobial Proteins - Diabetic nephropathy (DN) is one the most important complications of diabetes leading to end-stage renal disease. Dietary approaches have been considered to...     

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND)

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10^-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10^-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.     

The Renal Arterial Resistive Index and Stage of Chronic Kidney Disease in Patients with Renal Allograft

Objective

The study investigated the optimal threshold value of renal arterial resistive index as assessed by Doppler ultrasonography determining chronic kidney disease stage 4 or higher in patients with renal allograft.

Methods

In a cross-sectional study the renal arterial resistive index were obtained in interlobar arteries by Doppler ultrasonography in 78 patients with renal allograft. The stage of chronic kidney disease was determined by the estimated glomerular filtration rate equation.

Results

The median renal arterial resistive index was 0.61 (interquartile range, 0.56 to 0.66). We observed a significant association between renal arterial resistive index above the upper quartile and chronic kidney disease stage 4 or higher (relative risk, 4.64; 95% confidence interval, 1.71 to 12.55; p = 0.003 by Fisher’s exact test). Multivariate logistic regression analysis showed that renal arterial resistive indices (p = 0.02) and time since transplantation (p = 0.04), but not age, gender, or blood pressure were significantly associated with chronic kidney disease stage 4 or higher.

Conclusion

A renal arterial resistive index higher than 0.66 may determine the threshold value of chronic kidney disease stage 4 or higher in patients with renal allograft.     

替米沙坦联合阿托伐他汀治疗糖尿病肾病的疗效分析

目的:探讨替米坦联合阿托伐他汀治疗糖尿病肾病(DN)的疗效及机制.方法:选择糖尿病肾病60例,随机分为治疗组和对照组各30例,对照组单用替米沙坦治疗,治疗组应用替米沙坦联合阿托伐他汀治疗,疗程6个月.治疗前后观察TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值.结果:治疗前,两组TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值比较无明显差异(P>0.05),治疗6月后,与治疗前比较,除TC、TG外,两组患者的尿微量白蛋 白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6的值下降(P<0.01),治疗组的TC、TG、尿微量白蛋白(MALB)、24 h尿蛋白、Scr、BUN、C-反应蛋白、IL-6值较对照组低,差异有统计学意义(P<0.01).结论:采用替米沙坦和阿托伐他汀治疗糖尿病肾病具有降血脂、减少尿蛋白、改善肾功能、延缓病情进展的作用.