基于血浆醛固酮／肾素浓度比的联合策略在原发性醛固酮增多症中的筛查价值

目的：探讨最适于临床筛查原发性醛固酮增多症（ PA）的方案。方法收集疑诊PA的病例303例,分为PA组、原发性高血压组和无功能性肾上腺皮质意外瘤组。利用血浆醛固酮／肾素浓度比值（ ARR）绘制受试者工作特征（ ROC）曲线,获取最佳诊断界值。进一步对目前临床关于PA筛查的方案进行对比分析。结果立位ARR的ROC曲线下面积明显高于卧位ARR及立、卧位血浆肾素、醛固酮。立位ARR诊断PA的最佳诊断界值[（ pg／ml ）／（μIU／ml）]为43．45,两次立、卧位试验中至少一次立位ARR ＞43．45时诊断PA的灵敏度最高,达0．94;两次立位ARR均＜43．45时,其除外PA的灵敏度为0．74,特异度为0．94,准确度为0．81。结论在高危人群中筛查PA,推荐行两次立位血浆肾素、醛固酮浓度测定,在两次中只要有一次立位ARR＞43．45即需考虑PA可能,并进一步进行确诊试验以避免漏诊。     

A study of urinary and intracellular sodium and potassium, renin, aldosterone, and hypertension in blacks and indians in natal

The prevalence of hypertension in the urban black population in Sub-Saharan Africa is high and varies from 20% to 25%. In contrast, the prevalence of hypertension in the rural black is relatively low. In Natal the prevalence of hypertension in a large metropolitan city, Durban, is 25% in the adult Zulu, 17.2% in whites, and 14.2% in Indians. The prevalence of hypertension in the rural Zulu of Natal is 10%. Work on the pathogenesis of hypertension in the Zulu and Indian ethnic groups related to renin, aldosterone, dietary sodium and potassium, and intracellular sodium and potassium was virtually nonexistent. This review paper summarizes the salient features that were found. This paper is a summary of the work undertaken by Dr. S. Hoosen in partial fulfillment of the requirements for the Degree of Doctor of Medicine in the University of Natal, 1988.     

Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms

Discretionary control of Na⁺ excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine‐tuned in the aldosterone‐sensitive distal nephron by the activity of the epithelial Na⁺ channel (ENaC). Here, ENaC functions as a final effector of the renin–angiotensin–aldosterone system (RAAS) during negative feedback control of blood pressure. Mutations affecting ENaC activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na⁺ excretion. Recent evidence demonstrates that powerful signalling pathways function in parallel with the RAAS to modulate ENaC activity and blood pressure. An inclusive paradigm is emerging with respect to regulation of blood pressure where ENaC serves as a critical point of convergence for several important signalling systems that affect renal Na⁺ excretion. A robust inhibitory purinergic signalling system intrinsic to the distal nephron dynamically regulates ENaC through paracrine ATP signalling via the metabotropic P2Y₂ purinergic receptor to properly match urinary Na⁺ excretion to dietary Na⁺ intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na⁺ consumption. Loss of purinergic inhibition of ENaC increases blood pressure by causing inappropriate Na⁺ excretion. In contrast, stimulation of the P2Y₂ receptor promotes natriuresis and a decrease in blood pressure. Such observations identify purinergic signalling in the distal nephron as possibly causative, when dysfunctional, for certain forms of elevated blood pressure, and as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.     

Rethinking furosemide use for infants with bronchopulmonary dysplasia

Diuretics are commonly administered to infants with bronchopulmonary dysplasia (BPD) to improve respiratory function despite the absence of prospective data demonstrating long term benefits. While many potentially adverse effects of furosemide are known to clinicians, its direct and indirect impact on multiple pathophysiological processes need to be understood. While furosemide likely has a role in the management of infants with BPD, clinicians are encouraged to recognize these potential complications associated with furosemide administration. Specifically, a deeper understanding of the impact of diuretics on sodium metabolism neurohumoral regulation of cardiopulmonary physiology is required.     

疏血通注射液对原发性高血压患者RAAS活性的影响

目的：观察疏血通注射液对原发性高血压患者肾素血管紧张素醛固酮系统（RAAS）活性的影响。方法将入选的原发性高血压患者随机分为治疗组和对照组,观察两组治疗前后血压、血浆肾素（PRA）、血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）水平及血脂、血流液变学指标的变化。结果治疗后两组患者血浆 AngⅡ、ALD均较治疗前有所降低,治疗组降低更为明显（P＜0．05）,两组患者血浆肾素水平较治疗前升高,但差异无统计学意义（P＞0.05）。治疗组治疗后血压、血脂、血液流变学指标明显改善,与对照组相比差异有统计学意义（P＜0.05或P＜0.01）。结论疏血通注射液对原发性高血压患者 RAAS 活性有明显改善,可降低血浆AngⅡ、ALD的含量,改善血液流变学特性,有效降低血压。     

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin–angiotensin–aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31?mmHg; n?=?66) and the non-MS group (≤31?mmHg; n?=?195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0?±?5.4?ng/dl versus 12.2?±?8.7?ng/dl, p?p?=?0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6?±?4.4?mm Hg for the non-MS group and 18.9?±?4.9?mmHg for the MS group; p?相似文献   

The Role of Na+-H+ Exchanger Isoform 1 in Aldosterone-Induced Glomerulosclerosis in Vivo

Aldosterone is reported to promote fibrosis of multiple organs. Recent studies showed that Na⁺-H⁺ exchanger isoform 1 (NHE1) was involved in mineralocorticoid-induced tissue fibrosis. The present study examined the role of NHE1 in aldosterone-induced glomerulosclerosis in rats. SD male rats were subjected to 5/6 nephrectomy and divided into four groups: rats subjected to sham operation were used as control (SHAM group), 5/6 nephrectomy (SNX group), SNX treated with aldosterone via osmotic mini-pump (ALDO group), and SNX treated with aldosterone plus NHE1 inhibitor 5-(N, N-Dimethyl) amiloride hydrochloride (DMA) (ALDO+DMA group). The rats were sacrificed at the 12th week. We found that aldosterone treatment significantly increased kidney weight/body weight ratio and systolic blood pressure compared with SNX rats. Aldosterone also increased proteinuria and serum creatinine level. The NHE1 antagonist DMA significantly reversed the effect of aldosterone on proteinuria, but had no effect on the aldosterone associated hypertension and the elevation of serum creatinine. The remnant kidney of 5/6 nephrectomized rats exhibited increased glomerulosclerosis score, tubulointerstitial fibrosis, and tubular proteinaceous cast, which were significantly enhanced by aldosterone treatment. DMA treatment significantly reduced aldosterone-associated glomerulosclerosis, but failed to improve aldosterone-induced tubulointerstitial fibrosis and tubular proteinaceous cast. The aldosterone-induced increase in renal TGFβ1 and PCNA was significantly prevented by treatment with DMA. Our data showed that NHE1 inhibitor reduced aldosterone-induced glomerulosclerosis but not hypertension in 5/6 nephrectomized rats. The present study suggested that NHE1 contributed to aldosterone-induced-glomerulosclerosis and could be a potential therapeutic target for chronic kidney disease.     

Activation of the Endogenous Renin-Angiotensin-Aldosterone System or Aldosterone Administration Increases Urinary Exosomal Sodium Channel Excretion

Urinary exosomes secreted by multiple cell types in the kidney may participate in intercellular signaling and provide an enriched source of kidney-specific proteins for biomarker discovery. Factors that alter the exosomal protein content remain unknown. To determine whether endogenous and exogenous hormones modify urinary exosomal protein content, we analyzed samples from 14 mildly hypertensive patients in a crossover study during a high-sodium (HS, 160 mmol/d) diet and low-sodium (LS, 20 mmol/d) diet to activate the endogenous renin-angiotensin-aldosterone system. We further analyzed selected exosomal protein content in a separate cohort of healthy persons receiving intravenous aldosterone (0.7 μg/kg per hour for 10 hours) versus vehicle infusion. The LS diet increased plasma renin activity and aldosterone concentration, whereas aldosterone infusion increased only aldosterone concentration. Protein analysis of paired urine exosome samples by liquid chromatography-tandem mass spectrometry–based multidimensional protein identification technology detected 2775 unique proteins, of which 316 exhibited significantly altered abundance during LS diet. Sodium chloride cotransporter (NCC) and α- and γ-epithelial sodium channel (ENaC) subunits from the discovery set were verified using targeted multiple reaction monitoring mass spectrometry quantified with isotope-labeled peptide standards. Dietary sodium restriction or acute aldosterone infusion similarly increased urine exosomal γENaC_[112–122] peptide concentrations nearly 20-fold, which correlated with plasma aldosterone concentration and urinary Na/K ratio. Urine exosomal NCC and αENaC concentrations were relatively unchanged during these interventions. We conclude that urinary exosome content is altered by renin-angiotensin-aldosterone system activation. Urinary measurement of exosomal γENaC_[112–122] concentration may provide a useful biomarker of ENaC activation in future clinical studies.     

肾上腺腺瘤的影像组学研究进展

肾上腺腺瘤是临床上较常见的一种肿瘤。目前,影像组学在肾上腺良、恶性肿瘤,功能性肾上腺腺瘤亚型以及脂质性腺瘤和嗜铬细胞瘤的鉴别中取得初步进展,主要通过纹理分析、直方图分析等影像组学特征对肾上腺腺瘤展开研究,可有效评估肿瘤的异型性,可在临床决策上提供有效的帮助。此外,临床特征与影像组学特征结合的诺模图模型对功能性肾上腺腺瘤亚型具有良好的鉴别效果。现综述影像组学在肾上腺腺瘤的诊断和鉴别诊断以及治疗策略的疗效预测、监测和预后评估的研究现状、存在问题,并对未来进行初步展望。