Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion.
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.
Frassetto
L A
LA
Department of Medicine and General Clinical Research Center, University of California, San Francisco 94143, USA.
Nash
E
E
Morris
R C
RC
Sebastian
A
A
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000138:Acidosis / Q000150:complications / Q000188:drug therapy; D000368:Aged; D001639:Bicarbonates / Q000008:administration & dosage*; D002118:Calcium / Q000652:urine*; D003404:Creatinine / Q000652:urine; D004232:Diuretics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D007669:Kidney Calculi / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control; D011188:Potassium / Q000652:urine; D011189:Potassium Chloride / Q000008:administration & dosage*; D012964:Sodium / Q000652:urine; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*
D001639:Bicarbonates; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D011189:Potassium Chloride; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D002118:Calcium