Correspondence
Spironolactone in Addition to ACE Inhibition to Reduce Proteinuria in Patients with Chronic Renal Disease
N Engl J Med 2001; 345:925-926September 20, 2001
- Article
To the Editor:
Angiotensin-converting–enzyme (ACE) inhibitors have been shown to reduce proteinuria and slow the progression of renal disease.1 Although to date angiotensin II has been the focus of attention as the primary mediator of the renin–angiotensin–aldosterone system, several studies have raised the possibility that aldosterone itself has a role in mediating progressive renal disease.2,3 Pitt et al.4 showed that blockade of aldosterone receptors by spironolactone significantly reduced the risk of morbidity and death among patients with heart failure who were already receiving ACE inhibitors. The authors hypothesized that the benefits were not due to the hemodynamic effects of spironolactone but, instead, may have been due to an adverse effect of aldosterone on myocardial and vascular smooth-muscle cells. We tested the hypothesis that spironolactone may act along with ACE inhibitors in the kidney to reduce proteinuria.
Over the past 12 months, we studied eight patients with various renal diseases and persistent proteinuria (>1 g of protein per day), despite treatment with enalapril for more than 12 months. These patients were all receiving dipyridamole and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. No patient was receiving a nondihydropyridine calcium antagonist. Spironolactone, at a dose of 25 mg per day, was added to the medication, and protein excretion was measured in a 24-hour urine specimen obtained four weeks later.
The characteristics of the patients and the clinical findings are summarized in Table 1Table 1
Clinical Characteristics and Findings before and after Treatment with Spironolactone in Eight Patients.. After treatment with spironolactone, there was a 54 percent reduction in protein excretion (mean [±SD] value before spironolactone treatment, 3.81±2.50 g per day; mean value after treatment, 1.75±1.02 g per day). The benefit could not be explained by an effect of blood pressure, since there was no significant difference in blood pressure before and after the administration of spironolactone. There was also no significant difference in creatinine clearance before and after spironolactone treatment.Although it might be anticipated that any adverse effects of aldosterone would be blocked by using an ACE inhibitor or by angiotensin II–receptor blockade, this does not appear to be the case. ACE inhibition results in an acute decrease in the aldosterone concentration, but with continued use, the suppression is not sustained.5 One limitation of the renal protective effects of ACE inhibitors may thus be due to their inability to provide long-term suppression of aldosterone. We have shown that specific aldosterone blockade with spironolactone results in a reduction in proteinuria. Although the number of patients in our study was small, the results suggest that spironolactone therapy may be useful in patients with proteinuria and renal impairment, who still have proteinuria after treatment with ACE inhibitors.
5 ReferencesAnastasia Chrysostomou, B.M., B.S.
Gavin Becker, M.D., M.B., B.S.
Royal Melbourne Hospital, Parkville 3052, Australia
anastasiac@optusnet.com. au 1
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Pitt B . “Escape“ of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: implications for therapy. Cardiovasc Drugs Ther 1995;9:145-149
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