Addition of spironolactone to dual blockade of renin angiotensin system dramatically reduces severe proteinuria in renal transplant patients: an uncontrolled pilot study at 6 months.

Experimental and clinical data strongly suggest that aldosterone may contribute to proteinuria and progressive renal disease. In fact, an aldosterone antagonist seems to be effective for controlling proteinuria in native kidneys. However, there is little information about this approach in renal transplant patients, a population in whom the presence and amount of proteinuria represent risk factors for graft loss, cardiovascular disease, and death. The aim of our study was to evaluate whether addition of an aldosterone antagonist, spironolactone, provided an additional antiproteinuric effect to the angiotensin-converting enzyme inhibitor (ACEI) and angiotensin type I receptor antagonists (ARB). We evaluated the effects on severe proteinuria (4.4±1.4 g/d) at 6 months after prescription of spironolactone (25 mg/d) among 11 renal transplant patients with serum creatinine values less than 3 mg/dL who were under treatment with an ACEI plus an ARB. Patients were examined in the renal transplant outpatient clinic every week for the first month and twice a month thereafter. Nine patients showed a more than 50% (mean=81.5%) reduction in proteinuria not only early, but also sustained at 6 months (4.4±1.4 to 2.3±1.1 g/d) with a mild, nonsignificant deterioration in renal function (serum creatinine 1.6±0.32 to 1.7±0.54 mg/dL). This study showed that spironolactone decreased severe proteinuria among patients treated with an ACEI plus an ARB. This therapy is not recommended for patients with glomerular filtration rates below 40 mL/min. Therefore, it is suggested that using triple blockade of RAS is feasible in selected renal transplant patients to reduce proteinuria, although caution is required to avoid severe hyperkalemia.

González Monte E ，Andrés A ，Polanco N ，Toribio MJ ，Santana R ，Gutiérrez Martínez E ，González J ，Ramírez E ，Hernández A ，Morales E ，Praga M ，Morales JM ... -  《-》

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.

Furumatsu Y ，Nagasawa Y ，Tomida K ，Mikami S ，Kaneko T ，Okada N ，Tsubakihara Y ，Imai E ，Shoji T ... -  《HYPERTENSION RESEARCH》

Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II

Chrysostomou A ，Pedagogos E ，MacGregor L ，Becker GJ ... -  《-》

Renoprotective effect of early inhibition of the renin-angiotensin system in renal transplant recipients.

Montanaro D ，Gropuzzo M ，Tulissi P ，Vallone C ，Boscutti G ，Mioni R ，Risaliti A ，Baccarani U ，Adani GL ，Sainz M ，Bresadola F ，Mioni G ... -  《TRANSPLANTATION PROCEEDINGS》

Renin-angiotensin system dual blockade using angiotensin receptor plus aliskiren decreases severe proteinuria in kidney transplant recipients.

Renin-angiotensin system (RAS) blockade has cardioprotective and renoprotective effects in the general population; however, whether dual blockade using angiotensin-receptor blockade (ARB) plus a renin inhibitor, aliskiren, can minimize severe proteinuria in kidney transplant recipients remains undetermined. To analyze the efficacy and safety of dual blockade of the RAS with an ARB and aliskiren in kidney transplant recipients with severe proteinuria and creatinine concentration 2.5 mg/dL or less. This prospective study included 16 patients (mean age 56 years; 10 men [62%] who had undergone cadaveric renal transplantation between 1992 and 2004. Immunosuppression therapy included a calcineurin inhibitor in 9 patients (56%) or mammalian target of rapamycin inhibitor in 7 (44%), and mycophenolate mofetil in 15 (94%). All received high-dose ARB II (1.0-3.5 g/24 h) because of marked proteinuria, with poor response. Accordingly, 11 patients also received aliskiren, and in 5 who were receiving an angiotensin-converting enzyme inhibitor, therapy was changed to aliskiren. Mean (range) follow-up was 11 (3-18) months. At 3 months, proteinuria decreased by 40%, and at 6 months by 60%. In addition, mean blood pressure was decreased significantly. Renal function remained stable, as did the serum potassium concentration. A slight but significant decrease in hemoglobin concentration was observed, with no clinical repercussions. Dual blockade of the RAS with ARB II plus aliskiren therapy demonstrated an additive effect to decrease severe proteinuria and blood pressure in kidney transplant recipients. Neither relevant adverse effects in renal function nor anemia or hyperkalemia were observed. These findings might contribute to prolonging long-term kidney graft survival.

López V ，Martin M ，Cobelo C ，Aranda P ，Cabello M ，Sola E ，Gutierrez C ，Burgos D ，Martínez D ，Hernandez D ... -  《-》