氯化钾和碳酸氢盐对噻嗪类药物引起的尿钙排泄减少的比较作用。
Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion.
作者信息
Frassetto L A, Nash E, Morris R C, Sebastian A
机构信息
Department of Medicine and General Clinical Research Center, University of California, San Francisco 94143, USA.
出版信息
Kidney Int. 2000 Aug;58(2):748-52. doi: 10.1046/j.1523-1755.2000.00221.x.
BACKGROUND
The chronic low-grade metabolic acidosis that occurs in various renal disorders and in normal people, and that is related both to dietary net acid load and age-related renal functional decline, may contribute to osteoporosis by increasing urine calcium excretion. Administration of potassium (K) alkali salts neutralizes acid and lowers urine calcium excretion. Urine calcium excretion also can be reduced by the administration of thiazide diuretics, which are often given with supplemental K to avoid hypokalemia. We determined whether the K alkali salt potassium bicarbonate (KHCO3) and the thiazide diuretic hydrochlorothiazide (HCTZ) combined is more effective in reducing urinary calcium than KHCO3 alone or HCTZ combined with the conventionally coadministered nonalkalinizing K salt potassium chloride (KCl).
METHODS
Thirty-one healthy men and women aged 50 or greater were recruited for a four-week, double-blind, randomized study. After a baseline period of 10 days with three 24-hour urine and arterialized blood collections, subjects were randomized to receive either HCTZ (50 mg) plus potassium (60 mmol daily) as either the chloride or bicarbonate salt. Another 19 women received potassium bicarbonate (60 mmol) alone. After two weeks, triplicate collections of 24-hour urines and arterialized bloods were repeated.
RESULTS
Urinary calcium excretion decreased significantly in all groups. KHCO3 alone and HCTZ + KCl induced similar decreases (-0.70 +/- 0.60 vs. -0.80 +/- 1. 0 mmol/day, respectively). Compared with those treatments, the combination of HCTZ + KHCO3 induced more than a twofold greater decrease in urinary calcium excretion (-1.8 +/- 1.2 mmol/day, P < 0. 05). Both HCTZ + KHCO3 and KHCO3 alone reduced net acid excretion significantly (P < 0.05) to values of less than zero.
CONCLUSIONS
KHCO3 was superior to KCl as an adjunct to HCTZ, inducing a twofold greater reduction in urine calcium excretion, and completely neutralizing endogenous acid production so as to correct the pre-existing mild metabolic acidosis that an acid-producing diet usually induces in older people. Accordingly, for reducing urine calcium excretion in stone disease and osteoporosis, the combination of HCTZ + KHCO3 may be preferable to that of HCTZ + KCl.
背景
各种肾脏疾病以及正常人中出现的慢性轻度代谢性酸中毒,与饮食净酸负荷和年龄相关的肾功能衰退均有关联,可能通过增加尿钙排泄而导致骨质疏松。给予钾(K)碱性盐可中和酸并降低尿钙排泄。给予噻嗪类利尿剂也可降低尿钙排泄,噻嗪类利尿剂常与补充钾一起使用以避免低钾血症。我们确定了碱性钾盐碳酸氢钾(KHCO₃)与噻嗪类利尿剂氢氯噻嗪(HCTZ)联合使用在降低尿钙方面是否比单独使用KHCO₃或HCTZ与传统联合使用的非碱化钾盐氯化钾(KCl)更有效。
方法
招募了31名年龄在50岁及以上的健康男性和女性进行为期四周的双盲随机研究。在为期10天的基线期内,收集三次24小时尿液和动脉化血液样本后,受试者被随机分配接受HCTZ(50毫克)加钾(每日60毫摩尔),钾盐为氯化物或碳酸氢盐。另外19名女性单独接受碳酸氢钾(60毫摩尔)。两周后,重复收集三次24小时尿液和动脉化血液样本。
结果
所有组的尿钙排泄均显著降低。单独使用KHCO₃和HCTZ + KCl引起的降低相似(分别为-0.70±0.60与-0.80±1.0毫摩尔/天)。与那些治疗方法相比,HCTZ + KHCO₃联合使用使尿钙排泄的降低幅度超过两倍(-1.8±1.2毫摩尔/天,P < 0.05)。HCTZ + KHCO₃和单独使用KHCO₃均显著降低了净酸排泄(P < 0.05),使其值小于零。
结论
作为HCTZ的辅助药物,KHCO₃优于KCl,可使尿钙排泄降低两倍以上,并完全中和内源性酸生成,从而纠正产酸饮食通常在老年人中诱发的先前存在的轻度代谢性酸中毒。因此,对于降低结石病和骨质疏松症患者的尿钙排泄,HCTZ + KHCO₃联合使用可能比HCTZ + KCl联合使用更可取。