Response to Spironolactone Attenuates Oxidative Stress in Patients With Chronic Kidney Disease
We thank Renke et al1 for their interest in our recent article.2 The clinical study by Renke et al1 indicates that spironolactone, combined with angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, may act as an antioxidant, as measured by the urinary excretion of 15-F2t-isoprostane, without producing changes in systemic blood pressure. The results of our experimental chronic renal failure model showed that treatment with spironolactone has antioxidant effects in the heart. In addition, we observed that spironolactone was protective against heart hypertrophy without a significant antihypertensive effect. Several experimental and clinical studies have shown that combined double or triple renin-angiotensin-aldosterone blocking therapy can markedly attenuate the progression of renal injury, without significant hemodynamic effects. Furumatsu et al3 also demonstrated, in a 1-year randomized prospective study, that the triple combined therapy decreased proteinuria and urinary type IV collagen without reducing blood pressure. Although low doses of mineralocorticoid receptor antagonists had been used in several clinical studies, the emergence of hyperkalemia has been associated with the combined therapy, especially when kidney function is reduced.4
The therapeutic benefits of mineralocorticoid receptor blockers may result from a number of mechanisms, including suppression of proinflammatory molecules, inhibition of collagen synthesis, and reduction of oxidative stress.5 Therefore, and considering that blood pressure may not be the unique target to consider for the administration of mineralocorticoid receptor blockers, further studies are needed to clarify the roles of oxidative stress, proteinuria, and/or other markers of tissue damage that may be useful in monitoring the renoprotective effect of the combined therapy. The identification of such markers and their use in clinical settings would be helpful to define the minimal effective dosage and reduce the risk of adverse effects associated with the combined therapy.
Renke M, Tylicki L, Knap N, Rutkowski P, Neuwelt A, Larczyński W, Woźniak M, Rutkowski B. Spironolactone attenuates oxidative stress in patients with chronic kidney disease. Hypertension. 2008; 52: e132–e133.
Michea L, Villagrán A, Urzúa A, Kuntsmann S, Venegas P, Carrasco L, Gonzalez M, Marusic ET. Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and prevents oxidative stress in uremic rats. Hypertension. 2008; 52: 295–303.
Furumatsu Y, Nagasawa Y, Tomida K, Mikami S, Kaneko T, Okada N, Tsubakihara Y, Imai E, Shoji T. Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker. Hypertens Res. 2008; 31: 59–67.
Brown N. Aldosterone and vascular inflammation. Hypertension. 2008; 51: 161–167.