超声评分法及肾动脉阻力指数对胎儿肾积水预后的评价价值分析

目的:研究超声评分法及肾动脉阻力指数(RRI)对胎儿肾积水预后的评价价值。方法:将从2016年1月2019年1月经我院超声检查发现的孕晚期肾积水胎儿210例纳入研究,测定其肾实质厚度(RPT)、肾盂前后径(APD)以及肾盂肾盏形态,对上述各项超声检测指标进行评分,累计计算分值。此外,对所有胎儿的积水肾脏肾门部位的RRI值进行测定,并以受试者工作特征(ROC)曲线分析超声评分法与RRI值诊断胎儿肾积水预后类型的价值。结果:所有胎儿出生1年内分别行超声检查以及临床诊断,结果显示210例胎儿,共计420只肾脏,共发生285只肾积水,包括病理性肾积水84只(病理性组),非病理性肾积水201只(非病理性组)。病理性肾积水胎儿超声评分为13分的肾只数占比显著低于非病理性胎儿(P<0.05),而79分的肾只数占比显著高于非病理性胎儿(P<0.05)。病理性肾积水胎儿的平均RRI值为0.74±0.05,显著高于非病理性肾积水胎儿的0.63±0.02,差异有统计学意义(t=26.563,P=0.000)。超声评分法与RRI联合诊断病理性肾积水的曲线下面积(AUC)、敏感度、特异度、准确度均显著高于超声评分法或RRI单独诊断(P<0.05)。结论:超声评分法及RRI诊断对胎儿肾积水预后评价具有较重要的价值,值得临床推广应用。     

罗沙司他治疗肾性贫血的效果观察及对TSAT、Cys C及NOX2的作用分析

摘要 目的：探讨罗沙司他治疗肾性贫血的效果观察及对转铁蛋白饱和度（TSAT）、胱抑素C（Cys C）及NADPH氧化酶2（NOX2）的作用。方法：选择2019年12月到2020年12月在我院接受治疗的125例肾性贫血患者,采用随机数表法分为试验组（n=63）和对照组（n=62）。对照组给予重组人促红素治疗,试验组给予罗沙司他治疗。比较两组临床疗效、TSAT、Cys C、NOX2、红细胞计数（RBC）、血红蛋白（Hb）、血细胞比容（Hct）、铁蛋白（SF）、转铁蛋白（TRF）及铁调素（Hepc）水平变化情况及药物不良反应发生情况。结果：治疗后,两组总有效率比较差异显著（P<0.05）;治疗前,试验组和对照组血清TSAT、Cys C及NOX2比较无显著差异;治疗后,试验组和对照组血清TSAT随着时间的推移而升高,且试验组高于对照组,Cys C及NOX2随着时间的推移而升减降低,且试验组低于对照组,差异显著（P<0.05）;治疗前,试验组和对照组RBC、Hb、Hct检验结果比较无显著差异;治疗后,试验组和对照组RBC、Hb、Hct均随着时间的推移而升高,且试验组高于对照组,差异显著（P<0.05）;治疗前,试验组和对照组SF、TRF及Hepc检验结果比较无显著差异;治疗后,试验组和对照组血清SF、TRF均随着时间的推移而升高,且试验组高于对照组,Hepc随着时间的推移而下降,且试验组低于对照组,差异显著（P<0.05）;两组不良反应总发生率分别为4.76%、8.06%（P>0.05）。结论：在肾性贫血患者中应用罗沙司他效果显著,可能与其可有效改善血清TSAT、Cys C及NOX2水平有关,且不增加不良反应。     

Targeting Superoxide Dismutase to Renal Proximal Tubule Cells Attenuates Vancomycin-induced Nephrotoxicity in Rats

Vancomycin hydrochloride (VCM), a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). As it is known to induce renal dysfunction, the dose and the duration of its administration are limited. Moreover, the mechanism of VCM-induced renal dysfunction remains to be unclear. To evaluate the involvement of free radical on VCM-induced renal dysfunction, we carried out analysis with a hexamethylenediamine-conjugated superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Male Wistar rats (weighing 200-210 g) were intraperitonealy administered with 200 mg/kg of VCM twice a day for 7 days. AH-SOD 5 mg/kg/day was subcutaneously injected 5 min before every VCM injection. VCM induced renal injury dose-dependently. Biochemical analyses revealed that plasma levels of blood urea nitrogen and creatinine significantly increased in the VCM-treated group by an AH-SOD-inhibitable mechanism. VCM simultaneously elicited an increase of 8-OHdG levels and chemiluminescence intensity of free radical generation in the kidney. Histological examination revealed that VCM also elicited a marked destruction of glomeruli and necrosis of proximal tubules. AH-SOD inhibited these phenomena in the kidney. These results suggested that oxidative stress might underlie the pathogenesis of VCM-induced nephrotoxicity and targeting SOD and/or related antioxidants to renal proximal tubules might permit the administration of higher doses of VCM sufficient for eradication of MRSA without causing renal injury.     

Diagnostic Tests for Primary Renal Hypouricemia

Primary renal hypouricemia is a genetic disorder characterized by defective renal uric acid (UA) reabsorption with complications such as nephrolithiasis and exercise-induced acute renal failure. The known causes are: defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene. Diagnosis is based on hypouricemia (<119 μmol/L) and increased fractional excretion of UA (>10%). To date, the cases with mutations in hURAT1 gene have been reported in East Asia only. More than 100 Japanese patients have been described. Hypouricemia is sometimes overlooked; therefore, we have set up the flowchart for this disorder. The patients were selected for molecular analysis from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three transitions and one deletion (four times) in SLC22A12 gene and one nucleotide insertion in SLC2A9 gene in seven Czech patients were found. Three patients had acute renal failure and urate nephrolithiasis. In addition, five nonsynonymous sequence variants and three nonsynonymous sequence variants in SLC2A9 gene were found in two UK patients suffering from acute renal failure. Our finding of the defects in SLC22A12 and SLC2A9 genes gives further evidence of the causative genes of primary renal hypouricemia and supports their important role in regulation of serum urate levels in humans.     

Detection of Prothrombin and Osteopontin in a Renal Stone Found in a Hyperuricemic Patient Using 2D‐PAGE and LC‐MS Analysis

The liquid chromatography‐mass spectrometry (LC‐MS) following on from the two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) technique was applied for the analysis of proteins in a renal stone found in a hyperuricemic patient. This technique was sensitive enough to detect small quantities of proteins even in a renal stone.     

Association between urinary indicators of renal dysfunction and metal concentrations in workers chronically co-exposed to cadmium,zinc and lead

The study was carried out in 31 workers co-exposed to cadmium, lead and zinc fumes and dusts in a zinc ore refinery. Urinary cadmium, lead, zinc, β₂-M levels and NAG activities were determined to evaluate the possible dose-effect relationship between these parameters. A correlation was found between urinary cadmium, lead and zinc concentrations, and urinary β₂-M levels and NAG activities of the exposed group. A statistically significant increase was also observed for urinary NAG activity in exposed workers who had urinary cadmium concentrations > 2 μg g^?1 creatinine. However, in the same exposed group, the increment of β₂-M was not statistically significant. In conclusion, the present study thus confirms the earlier observations and may suggest the notion that the urinary NAG seems to be a more sensitive indicator than urinary β₂-M level in early stages of renal injury of moderately cadmium co-exposure with lead and zinc even at urinary cadmium concentration as low as 2 μg g^?1 creatinine. When the earlier studies on the irreversibility of cadmium-induced tubular dysfunction and the present results were taken into consideration, the present health-based biological limit proposed by the WHO (5 μg g^?1 creatinine) seems to be high for the occupational exposure to cadmium.     

肾移植术后HCMV感染与淋巴细胞亚群及肾功能的相关性

目的：肾移植患者由于术前透析及术后服用免疫抑制剂,显著增加了人巨细胞病毒（Humancytomegalovirus,HCMV）原发感染和潜伏感染被激活的机会。观察HCMV感染情况与血T淋巴细胞亚群及肾功能的变化,以探讨其相关性及临床意义。方法：跟踪收集40例肾移植患者术前、术后血标本,应用RT-PCR技术检测HCMV,流式细胞术检测淋巴细胞亚群,结合肾功能判断是否发生急性排斥或移植肾功能恢复延迟。结果：肾移植术后HCMV感染率为52．5％,10例出现症状性感染（25％）,出现阳性时间35．7±15．3天。症状性感染组CD3-bCD4＋的水平和CD4＋／CD8＋的比值较无活动性感染组和正常对照组均降低,CD8＋水平较其他组升高,差异有显著性意义（P〈0．05）。无症状性活动感染者与无活动性感染者各指标比较差异无显著性。活动性感染组急性排斥或移植肾功能恢复延迟发生8例（38．1％）,无活动性感染组发生1例（5．2％）,差异具有统计学意义（x^2=6．15,P〈0．05）。结论：肾移植术后HCMV感染能显著引起T淋巴细胞亚群变化,尤其是CD4＋／CD8＋。并与急性排斥或移植肾功能恢复延迟密切相关联,在其发生发展中可能起着重要的作用。三者相互联系、相互作用、互为因果,对进一步机制的研究及临床诊断治疗、预后方面有一定意义。     

Differential role of cyclooxygenase-1 and -2 on renal vasoconstriction to α1-adrenoceptor stimulation in normotensive and hypertensive rats

Aims

Hypertension is associated with the impairment of renal cyclooxygenase (COX) activity, which regulates vascular tone, salt and water balance and renin release. We aimed to evaluate the functional role of COX isoforms in kidneys isolated from spontaneously hypertensive rats (SHR) after α₁-adrenoceptor (α₁-AR) stimulation.

Main methods

Male six-month-old SHR and normotensive Wistar-Kyoto rats (WKY) were used. The kidneys were isolated to measure perfusion pressure and COX-1- or COX-2-derived prostanoids in response to α₁-AR activation.

Key findings

The basal perfusion pressure was higher in SHR kidneys compared with WKY kidneys (95 ± 11 vs. 68 ± 6 mm Hg, P < 0.05). Phenylephrine induced a greater vasopressor response in SHR kidneys (EC₅₀ of 1.89 ± 0.58 nmol) than WKY kidneys (EC₅₀ of 3.30 ± 0.54 nmol, P < 0.05 vs. SHR). COX-1 inhibition decreased the α₁-AR-induced vasoconstrictor response in WKY but did not affect SHR response, while COX-2 inhibition diminished the response in SHR. Both basal prostacyclin (PGI₂) and thromboxane A₂ (TxA₂) values were higher in SHR kidney perfusates (P < 0.05) and were reduced by COX-1 and COX-2 inhibitors in both strains. Furthermore, phenylephrine increased PGI₂ through COX-2 in WKY and through COX-1 in SHR, but the agonist did not significantly modify TxA₂ in both strains.

Significance

The data suggest that COX-1contributes to vasoconstrictor effects in WKY kidneys and that COX-2 has the same effect in SHR kidneys. The results also suggest that basal release of COX-2-derived vasoconstrictor prostanoids is involved in renal vascular hypersensitivity in SHR.     

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D₅R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D₅R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D₅R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D₅R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D₅R trafficking and that SNX1 depletion results in D₅R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension.     

Determination of an Angiotensin II-regulated Proteome in Primary Human Kidney Cells by Stable Isotope Labeling of Amino Acids in Cell Culture (SILAC)

Angiotensin II (AngII), the major effector of the renin-angiotensin system, mediates kidney disease progression by signaling through the AT-1 receptor (AT-1R), but there are no specific measures of renal AngII activity. Accordingly, we sought to define an AngII-regulated proteome in primary human proximal tubular cells (PTEC) to identify potential AngII activity markers in the kidney. We utilized stable isotope labeling with amino acids (SILAC) in PTECs to compare proteomes of AngII-treated and control cells. Of the 4618 quantified proteins, 83 were differentially regulated. SILAC ratios for 18 candidates were confirmed by a different mass spectrometry technique called selected reaction monitoring. Both SILAC and selected reaction monitoring revealed heme oxygenase-1 (HO-1) as the most significantly up-regulated protein in response to AngII stimulation. AngII-dependent regulation of the HO-1 gene and protein was further verified in PTECs. To extend these in vitro observations, we overlaid a network of significantly enriched gene ontology terms from our AngII-regulated proteins with a dataset of differentially expressed kidney genes from AngII-treated wild type mice and AT-1R knock-out mice. Five gene ontology terms were enriched in both datasets and included HO-1. Furthermore, HO-1 kidney expression and urinary excretion were reduced in AngII-treated mice with PTEC-specific AT-1R deletion compared with AngII-treated wild-type mice, thus confirming AT-1R-mediated regulation of HO-1. Our in vitro approach identified novel molecular markers of AngII activity, and the animal studies demonstrated that these markers are relevant in vivo. These interesting proteins hold promise as specific markers of renal AngII activity in patients and in experimental models.