Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers

Accidental or intentional ingestion of glyphosate surfactant-based herbicides, like Roundup^®, leads to nephrotoxicity as well as death. In this study, a panel of kidney injury biomarkers was evaluated in terms of suitability to detect acute kidney injury and dysfunction. The Roundup^® intoxication model involved oral administration of glyphosate to rats at dose levels of 250, 500, 1200 and 2500 mg/kg. Urinary and plasma biomarker patterns were investigated at 8, 24 and 48 h after dosing. Biomarkers were quantified by absolute concentration; by normalising to urine creatinine; and by calculating the excretion rate. The diagnostic performances of each method in predicting of acute kidney injury were compared. By Receiver Operating Characteristic (ROC) analysis of the selected biomarkers, only urinary kidney injury molecule-1 (KIM-1) best predicted histological changes at 8 h (best cut-off point > 0.00029 μg/ml). Plasma creatinine performed better than other biomarkers at 24 h (best cut-off point > 0.21 mg/dl). Urinary KIM-1 was the best early biomarker of kidney injury in this glyphosate-induced nephrotoxicity model.     

血清胱抑素C和尿微量白蛋白联合检测对高血压早期肾损害的诊断价值

目的：探讨血清胱抑素C（Cys-C）和尿微量白蛋白（UmAlb）联合检测对高血压早期肾损害的诊断价值。方法选择151例高血压患者,其中,高血压1级62例,高血压2级48例,高血压3级41例。另选取同期在本院作健康体检者60例作为对照组。分别采血及24 h尿液检测Cys-C和UmAlb水平并进行比较分析。结果高血压1级、2级、3级三组患者血清Cys-C及UmAlb水平均显著高于对照组（P均〈0.01）;高血压1级、2级、3级三组间Cys-C和UmAlb水平比较,差异均有显著统计学意义（高血压1级组〈2级组〈3级组, P均〈0.01）。结论血清Cys-C和UmAlb均为反映高血压早期肾功能损害的敏感指标,两者联合检测对高血压早期肾损害的诊断有重要价值。     

前列地尔对早期糖尿病肾病患者血清Cys-C、TNF-α及IL-6的影响

目的观察前列地尔注射液对早期糖尿病肾病（DN）患者血清胱抑素C（Cys-C）、肿瘤坏死因子-α（TNF-α）及白细胞介素-6（IL-6）的影响。方法将106例早期DN患者随机分为对照组和观察组,每组53例。对照组：给予饮食、运动、胰岛素、控制血压等常规方法;观察组：在对照组基础上,给予前列地尔注射液,疗程2周;比较2组患者血清Cys-C、TNF-α及IL-6变化。结果对照组血清Cys-C、TNF-α及IL-6无显著变化（P〉0.05）;观察组2周后血清Cys-C、TNF-α及IL-6明显低于2周前及对照组水平（P〈0.05）。结论前列地尔注射液能明显降低DN患者血清Cys-C、TNF-α及IL-6,对肾脏发挥一定保护作用。     

慢性肾脏病患者血浆中介素的变化及其与同型半胱氨酸、胱抑素-C的相关性研究

目的：探讨中介素（IMD）在慢性肾脏病（CKD）时的水平变化及其与同型半胱氨酸（Hcy）、胱抑素-C（Cyc-C）的相关性。方法检测30例正常人和147例CKD患者血浆IMD、肾上腺髓质素（ADM）和转化生长因子β1（TGF-β1）的浓度,患者根据肾小球滤过率分为1～5期,分析三者在不同分期的变化及其与Hcy、Cyc-C的相互关系。结果（1）随着CKD分期的不同,患者β2微球蛋白、Cyc-C、Hcy、GFR、ADM、TGF-β1水平与对照组相比,差异均有统计学意义（P＜0.05）,IMD含量差异无统计学意义（P＞0.05）。（2）GFR＞60 ml/min的CKD患者中不同病因类型中IMD的含量：与对照组相比,血浆IMD含量在肾病综合征组、IgA肾病组水平明显升高,差异有统计学意义（P＜0.05）;各组ADM含量与对照组相比,差异无统计学意义。各组TGF-β1含量均明显高于对照组（P＜0.05）。（3）GFR＞60 ml/min的CKD患者中：IgA肾病组：IMD与Cys-C、Hcy均呈显著正相关（r＝0.900、0.900,P均＜0.05）。结论血浆IMD、ADM和TGF-β1在CKD进展中呈现一定变化趋势,尤其在IgA肾病早期变化明显,且与血管损伤因子Hcy、Cyc-C具有正相关性,提示IMD和ADM可能参与CKD血管损伤的病理过程;而TGF-β1在肾纤维化过程中的变化,反映了机体自我调节的作用。     

Cystatin-C and inflammatory markers in the ambulatory elderly

Purpose

Inflammatory factors are elevated in persons with severe renal dysfunction, but their association across all levels of renal function is unclear. We compared cystatin-C, a novel marker of renal function, with creatinine and estimated glomerular filtration rate (eGFR) as predictors of C-reactive protein and fibrinogen levels.

Methods

This study is a cross-sectional analysis to evaluate cystatin-C, creatinine, and eGFR as predictors of the inflammatory markers C-reactive protein and fibrinogen. Participants included 4637 ambulatory elderly patients from the Cardiovascular Health Study. Multivariate linear regression was used to determine the independent associations of each renal function measurement with the inflammatory marker outcomes.

Results

After adjustment for confounding factors, cystatin-C was correlated with both C-reactive protein (coefficient = 0.13; 95% confidence interval: 0.10-1.16, P <.0001) and fibrinogen levels (0.15; 0.13-0.18, P <.0001). Associations were larger than those for creatinine and C-reactive protein (0.05; 0.02-0.07, P = .003) or fibrinogen (0.07; 0.04-0.10, P <.0001). Adjusted levels of C-reactive protein increased incrementally across quintiles of cystatin-C, from a median of 2.2 mg/L in quintile 1 to 3.7 mg/L in quintile 5. In contrast, both C-reactive protein and fibrinogen had U-shaped associations with quintiles of creatinine and eGFR, because the inflammatory markers were equivalently elevated in quintiles 1 and 5.

Conclusions

The finding of a significant linear association of cystatin-C and inflammation markers suggests that even small reductions in renal function may be associated with adverse pathophysiologic consequences.     

血清胱抑素C评价肾小球滤过率的临床意义

目的探讨应用血清胱抑素C(CysC)判断肾小球滤率的价值。方法对235例患者分别用乳胶增强免疫透射比浊法测定血清CysC的浓度及使用苦味酸速率法和酶学传导速率法测定血清肌酐(Scr)、尿素氮(BUN),以99Tcm-DTPA清除率测得的GFR作为评价的标准,分析CysC、Scr、BUN和GFR之间的相关性;按照GFR值将患者分4组:A组GFR≥90 ml(/min.1.73 m2),B组60~89 ml/(min.1.73 m2),C组30~59 ml(/min.1.73 m2),D组<30 ml(/min.1.73 m2),依据单侧肾小球滤过率GFR<40 ml/min(60岁以上<35 ml/min)为肾滤过功能减退依据,比较CysC、Scr、BUN 3指标诊断各组分肾GFR下降敏感度与特异度。结果 235例患者,随着GFR下降,血清CysC、BUN、Scr均逐渐升高(P<0.01),血清CysC与GFR之间呈负相关(r=-0.649,P<0.01),血清CysC与Scr、BUN之间呈正相关(r=0.850、r=0.874,P<0.01)。A、B、C组患者血清CysC诊断分肾滤过功能下降敏感度分别为58.82%、76.56%和95.51%,均优于Sc(rP<0.01)、BUN(P<0.05);A、B组患者血清CysC诊断分肾滤过功能下降特异度低于Scr、BUN(P<0.05)。结论测定血清胱抑素C的浓度用来评价肾小球滤过功能是一种可行、敏感的指标,测定方法简便,对预测早期肾损害迅速灵敏,值得临床推广应用。     

中性粒细胞明胶酶相关载脂蛋白、肾损伤分子-1及胱抑素-C对ICU脓毒症患者并发急性肾损伤的诊断效能

目的探讨中性粒细胞明胶酶相关载脂蛋白(NGAL)、肾损伤分子-1(KIM-1)及胱抑素-C(Cys-C)对ICU脓毒症患者并发急性肾损伤(AKI)的诊断效能。方法选择2018—2019年辽宁省人民医院收治的脓毒症患者114例,依据患者是否出现AKI分为损伤组61例和非损伤组53例。以双抗体夹心酶标免疫分析法检测患者不同时间点NGAL、KIM-1和Cys-C水平,评估三者对AKI的诊断效能。结果两组不同时间点NGAL、KIM-1和Cys-C水平差异均有统计学意义(P<0.05)。三种标志物单独检测的诊断效能以KIM-1最佳,三种标志物联合检测的诊断效能优于单一标志物检测。结论血清NGAL、KIM-1和Cys-C均可早期预测脓毒症患者出现AKI,推荐三种标志物联合检测,以提高诊断效能。     

Correlation of Cystatin-C with Glomerular Filtration Rate by Inulin Clearance in Pregnancy

Objective. To test utility of cystatin-C as a marker of glomerular filtration rate during pregnancy, we performed serial correlations with inulin clearance during pregnancy and postpartum. Methods. Twelve subjects received inulin infusions and serum cystatin-C at three time points. Pearson's correlation coefficient was calculated. Results. Cystatin-C levels ranged 0.66–1.48 mg/L during pregnancy, and 0.72–1.26 mg/L postpartum. Inulin clearance ranged 130–188 mL/min during pregnancy, and 110–167 mL/min postpartum. Cystatin-C did not correlate with inulin clearance at any time point. Conclusion. Serum cystatin-C did not correlate with inulin clearance during pregnancy or postpartum.     

维持透析的终末期肾脏病患者血清胱抑素-C与肌酐的相关性分析

目的分析维持性非卧床腹膜透析(CAPD)患者和维持性血液透析(HD)患者的血清胱抑素-C(Cys-C)水平,比较不同透析方式对Cys-C的影响;并进一步探讨Cys-C与血肌酐(Scr)的相关性,探索判断残存肾功能的新型标志物。方法选取肾内科病情稳定的CAPD患者160例归为腹膜透析组,病情稳定的HD患者80例归为血液透析组。两组患者每1～3个月抽血一次,采用胶乳凝聚法检测血清Cys-C浓度,采用苦味酸法测定血清Scr,比较两组患者的Cys-C、Scr水平,并分析两指标的相关性。结果腹膜透析组血清Scr、Cys-C水平均显著高于血液透析组(P<0.01),两个指标的比值进一步比较,腹膜透析组仍高于血液透析组(P<0.05)。对腹膜透析组、血液透析组及两组合并行Pearson相关分析,发现Scr和Cys-C呈线性正相关(P<0.01)。进一步行简单线性回归,回归方程估计为:Scr=389.93+98.49Cys-C。结论腹膜透析对终末期肾脏病(ESRD)患者Cys-C的清除能力低于血液透析;Cys-C可作为判断维持透析的ESRD患者残存肾功能的新型标志物。