Sebastian A, Sutton J M, Hulter H N, Schambelan M, Poler S M
Kidney Int. 1980 Dec;18(6):762-73. doi: 10.1038/ki.1980.195.
Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 to 875 micrograms/day, administered orally. Creatinine clearance averaged 98 +/- 8 ml/min/1.73 m2. Following a control period, mineralocorticoid replacement with fludrocortisone (100 to 200 micrograms/day) was either discontinued (N = 3) or initiated (N = 2). In an additional patient, mineralocorticoid replacement was initiated and sustained (5 days) by continuous i.v. infusion of aldosterone, at a dose approximating the normal secretion rate (120 micrograms/day). Net acid excretion (NAE) and plasma total carbon dioxide decreased in each patient in whom mineralocorticoid was discontinued and increased in each patient in whom mineralocorticoid was initiated. The cumulative change in NAE (sigma delta NAE) independent of direction averaged 66 +/- 20 mEq (P less than 0.05) by the fifth experimental day in the six patients, and the corresponding change in plasma total CO2 averaged 1.2 +/- 0.3 mmoles/liter (P less than 0.02). The magnitude of sigma delta NAE correlated with the basal rate of NAE (r = 0.87, P less than 0.05), which averaged 0.9 +/- 0.1 mEq/kg body wt per day. The change in plasma total CO2 correlated with sigma delta NAE (r = 0.83, P less than 0.05). The changes in NAE correlated positively with the corresponding changes in sodium balance and negatively with the corresponding changes in potassium balance. These findings provide the first evidence that renal acidification is under tonic stimulation by mineralocorticoid at levels not exceeding those in normal subjects ingesting acid-producing diets of normal sodium and potassium content. The extent to which the tonic stimulation of renal acidification is mediated by a direct effect of mineralocorticoid on renal hydrogen ion transport or by an indirect effect dependent on altered renal sodium and/or potassium transport requires further investigation. The findings implicate mineralocorticoid deficiency as a significant renal acidosis-producing condition not dependent on the presence of renal disease or glucocorticoid deficiency, and potentially amplified when endogenous acid production is increased by diet or disease.
对6例肾上腺切除患者进行了慢性平衡研究，以调查在不存在糖皮质激素缺乏或实质性肾脏疾病的情况下，盐皮质激素缺乏对肾脏及全身酸碱平衡的影响。通过口服地塞米松（750至875微克/天）持续补充糖皮质激素。肌酐清除率平均为98±8毫升/分钟/1.73平方米。在一个对照期后，3例患者停止使用氟氢可的松（100至200微克/天）进行盐皮质激素替代，2例患者开始使用。另外1例患者通过持续静脉输注醛固酮开始并维持（5天）盐皮质激素替代，剂量接近正常分泌率（120微克/天）。在停止盐皮质激素替代的每位患者中，净酸排泄（NAE）和血浆总二氧化碳均下降，而在开始盐皮质激素替代的每位患者中则上升。在6例患者中，到实验第5天，与方向无关的NAE累积变化（∑ΔNAE）平均为66±20毫当量（P<0.05），血浆总二氧化碳的相应变化平均为1.2±0.3毫摩尔/升（P<0.02）。∑ΔNAE的幅度与NAE的基础速率相关（r=0.87，P<0.05），基础速率平均为0.9±0.1毫当量/千克体重·天。血浆总二氧化碳的变化与∑ΔNAE相关（r=0.83，P<0.05）。NAE的变化与钠平衡的相应变化呈正相关，与钾平衡的相应变化呈负相关。这些发现首次证明，在不超过摄入正常钠钾含量产酸饮食的正常受试者水平的情况下，盐皮质激素对肾酸化有持续刺激作用。盐皮质激素对肾氢离子转运的直接作用或依赖于肾钠和/或钾转运改变的间接作用在多大程度上介导肾酸化的持续刺激，尚需进一步研究。这些发现表明，盐皮质激素缺乏是一种不依赖于肾脏疾病或糖皮质激素缺乏的显著的肾性酸中毒产生情况，并且当饮食或疾病使内源性酸产生增加时可能会加剧。
