Enalapril causes low urinary citrate excretion in normal human volunteers.
ASN 30th Annual Meeting, San Antonio
J Am Soc Nephrol (Sep) 8:129A 1997
At last year's meeting, the authors demonstrated that enalapril lowered urinary citrate excretion in rats. Though there are no data yet suggesting that ACE inhibitors are associated with stone formation, it was important to investigate whether this effect occurred in humans as well. The authors administered 10 mg of enalapril bid to 10 healthy volunteers for 10 days and measured urinary and serum electrolytes after 3 days of a standardized diet. Enalapril in these patients caused no changes in plasma pH or electrolytes, or in urinary volume, pH, electrolytes, oxalate, uric acid or NH3 excretion. Urinary citrate excretion fell from 327 ± 78 mg/d to 276 ± 61 mg/d.
Comment: This effect to lower urinary citrate was rather small, and in these normal individuals not likely to be associated with stone formation. The effect of this class of drug on patients with pre-existing stone disease or other tubular disorders is not known. The authors urge caution in using ACEi in stone formers.
There are several possible etiologies for this effect. By inhibiting Na/H exchange, ACEi may lead to a decrease in intracellular pH, which stimulates citrate excretion. Reduction of aldosterone secretion could lead to a lowering of urinary pH and metabolic acidosis (like so-called Type IV RTA) by reducing urinary NH4 excretion, which also could increase citrate reabsorption. ACE inhibition may also lead to stimulation of renal cortical ATP citrate lyase which would increase citrate metabolism (to acetyl CoA and oxaloacetate) and lower urinary citrate excretion. Hypokalemia has a similar effect to reduce citrate excretion, by leading to a reduction of intracellular pH.
The high prevalence of ACE inhibitor usage has not yet led to even anecdotal reports that these drugs are associated with stone formation. It would certainly be interesting to evaluate urinary citrate in patients with known stone disease who are treated with ACEi for hypertension. (David S. Goldfarb, M.D., NYU School of Medicine)
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ASN 30th Annual Meeting, San Antonio
Nephrolithiasis : Renal Stones: Treatment
H: Drug therapy : ACE inhibitors