A two-year dietary carcinogenicity study of cyadox in Sprague-Dawley rats

To investigate the potential carcinogenicity of cyadox, an antimicrobial agent, four groups of Sprague-Dawley rats (50 rats/sex/group) were fed diets containing cyadox (0, 200, 600 or 2000 mg/kg) for up to two years. There were significant decreases in body weight, feed intake and feed efficiency in both genders during most of the period in the 2000 mg/kg group. Significant decreases in serum ALT were observed in the 2000 mg/kg group at weeks 52, 78 and 104. For the control, 200, 600, and 2000 mg/kg groups, the tumor incidence in females was 33.3%, 37.2%, 40.0% and 19.0%, while it in males it was 18.9%, 2.6%, 17.1% and 13.6%, respectively. At histopathology, no increases in tumor incidence were attributed to treatment with cyadox. The mild swelling and fatty degeneration in hepatocytes, and mild swelling and tubular necrosis in the kidney were observed in 2000 mg/kg group. The no-observed-effect-level (NOEL) for carcinogenicity of cyadox fed to rats was 2000 mg/kg diet (132.18–156.28 mg/kg b.w./day). In conclusion, cyadox was not carcinogenic to rats with the liver and kidney as the target organs, and the side chain may be involved in toxicity and carcinogenicity mediated by QdNOs.     

托伐普坦治疗慢性心力衰竭的疗效及安全性

 目的 探讨托伐普坦治疗慢性心力衰竭(chronic heart failure,CHF)患者的疗效及安全性。方法 将60例CHF患者随机分为对照组与观察组,每组30例。对照组给予常规抗心力衰竭治疗,观察组在对照组基础上加用托伐普坦治疗。于治疗前、治疗后7 d检测24 h尿量、血钠、血钾、尿素氮、肌酐、尿酸、B型利钠肽(BNP)、左室射血分数(LVEF)并评价疗效。结果 治疗7 d 后,与治疗前相比,两组患者24 h尿量、血钠明显改善,BNP下降,差异有统计学意义(P<0.05)。与对照组治疗后比较,观察组尿素氮、肌酐明显下降,LVEF明显升高,差异有统计学意义(P<0.05);但尿酸、血钾未见明显变化。观察组总有效率(90.0%)高于对照组(63.3%),差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 托伐普坦可有效改善CHF患者临床症状,纠正低钠血症,改善心肾功能,且不会引起电解质紊乱,不良反应少。     

尿液肾功能指标和血清半胱氨酸蛋白酶抑制剂 Ｃ 对早期糖尿病肾病的 诊断价值及其风险评估模型的建立

摘要：目的 探讨尿液肾功能指标和血清半胱氨酸蛋白酶抑制剂 Ｃ（ＣｙｓＣ）对早期糖尿病肾病（ＤＮ）的诊断价值，同时构建早 期 ＤＮ 风险评估列线图模型。 方法 回顾性分析本院 ２０１９ 年 １ 月至 ２０２１ 年 １２ 月收治的 ８７３ 例 ２ 型糖尿病（Ｔ２ＤＭ）患者，根 据尿微量白蛋白／ 肌酐比值（ｕｍＡＣＲ）分为 Ｔ２ＤＭ 组（ｎ ＝ ３８７）、早期 ＤＮ（ＤＮ１）组（ｎ ＝ ３１３）和临床 ＤＮ（ＤＮ２）组（ ｎ ＝ １７３），比较 各组人群临床资料以及肾功能指标，并采用 ＲＯＣ 曲线分析各指标单独和联合诊断效能，用 Ｒ 软件绘制相关分析热图，多因素 Ｌｏｇｉｓｔｉｃ 回归分析 ＤＮ 发生的独立危险因素，建立 ＤＮ 诊断模型并采用 Ｂｏｏｔｓｔｒａｐ 法验证。 结果 血清 ＣｙｓＣ、ｅＧＦＲ、尿 α１ －微球 蛋白（ｕα１ ?ＭＧ）、尿 β２ 微球蛋白（ｕβ２ ?ＭＧ）、尿免疫球蛋白 Ｇ（ｕＩｇＧ）、尿转铁蛋白（ｕＴｒＦ）和尿微量清蛋白（ ｕｍＡｌｂ）水平：ＤＮ２ 组 ＞ＤＮ１ 组＞Ｔ２ＤＭ 组，差异均有统计学意义（Ｐ 均＜０．０５）；多指标联合诊断的 ＲＯＣ 曲线下面积（ＡＵＣ ＲＯＣ ）为 ０．９０４，敏感性和特异 性分别为 ７５．４％和 ９５．１％，均高于各指标单独检测效能。 ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 与 ｕｍＡＣＲ 呈正相关，与 ｅＧＦＲ 呈 负相关（Ｐ 均＜０．００１）。 多因素 Ｌｏｇｉｓｔｉｃ 回归分析结果显示，年龄、ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 是 ＤＮ 的独立危险因素 （Ｐ 均＜０．０５），列线图评估 ＤＮ 风险的一致性指数（Ｃ?ｉｎｄｅｘ）为 ０．９１９，区分度良好；校准图显示预测风险发生率与实际风险发生 率有良好的一致性。 结论 ｕα１ ?ＭＧ、ｕβ２ ?ＭＧ、ｕＩｇＧ、ｕＴｒＦ 和 ＣｙｓＣ 联合对早期 ＤＮ 具有较高诊断价值，基于以上指标所建立的 个体化预测 ＤＮ 发生风险的列线图模型具有良好的准确度与区分度，对 Ｔ２ＤＭ 并发 ＤＮ 高风险人群的早期诊断和干预提供了 可靠的依据。     

Submaximal Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Dosing Among Persons With Proteinuria

For persons with proteinuria, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are treatment mainstays for reducing kidney disease progression. Guidelines for managing hypertension and chronic kidney disease recommend titrating to the maximum ACEi/ARB dose tolerated. Using deidentified national electronic health record data from the Optum Labs Data Warehouse, we examined ACEi/ARB dosing among adults with proteinuria—defined as either a urine albumin to creatinine ratio of 30 mg/g or greater or a protein to creatinine ratio of 150 mg/g or greater—who were prescribed an ACEi/ARB medication between January 1, 2017, and December 31, 2018. Among 100,238 included patients (mean age, 65.1 years; 49,523 [49.4%] female), 29,883 (29.8%) were taking maximal ACEi/ARB doses. Among 74,287 patients without potential contraindications to dose escalation (systolic blood pressure <120 mm Hg, estimated glomerular filtration rate <15 mL/min per 1.73 m², serum potassium level greater than 5.0 mEq/L, or acute kidney injury within the prior year), the frequency of maximal ACEi/ARB dosing was 32.3% (24,025 patients). In adjusted analyses, age less than 40 years, female sex, Hispanic ethnicity, lower urine albumin to creatinine ratio, lack of diabetes, heart failure, lower blood pressure, higher serum potassium level, and prior acute kidney injury were associated with lower odds of maximal ACEi/ARB dosing. Having a prior nephrologist visit was not associated with maximal dosing. Our results suggest that greater attention toward optimizing the dose of ACEi/ARB therapy may represent an opportunity to improve chronic kidney disease care and reduce excess morbidity and mortality associated with disease progression.     

Documento de información y consenso para la detección y manejo de la enfermedad renal crónica

Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific societies, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options.The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology.The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.     

Chronic β-adrenergic stimulation increases ErbB receptors and cell proliferation in mouse kidney

Although the sympathetic nervous system is involved in injury caused to the kidney by several stressors such as hypertension or ischemia/reperfusion, little is known about the effect of chronic adrenergic stimulation in the kidneys. Upon injury, however, the kidney possesses a high capacity for tubular cell regeneration and functional recovery. The ErbB1 receptor and its ligands play an essential role in this process. We studied the effects of chronic isoproterenol (ISO) administration (β-adrenoceptor agonist) in the mouse kidney. ISO induced a moderate and reversible loss of kidney weight and protein content that was not associated with renal dysfunction. We observed an increase in tubular cell proliferation (bromodeoxyuridine labeling) in ISO-treated mice in both the outer and inner cortex. ErbB1 (epidermal growth factor receptor) along with ErbB2 and ErbB3 (neuregulin receptor) were transiently overexpressed in ISO-treated mice, with an increase in protein but not mRNA content. All receptors were localized in the same nephron segments and cell types. Immunoprecipitation studies after epidermal growth factor or neuregulin-1β stimulation showed dynamic interaction of all four ErbB receptors. Therefore, we conclude that ErbB receptors may cooperate in the response to chronic β-adrenergic stimulation.