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
E
Servicio de Nefrología, Hospital 12 de Octubre, Madrid, Spain.
Andrés
A
A
Polanco
N
N
Toribio
M J
MJ
Santana
R
R
Gutiérrez Martínez
E
E
González
J
J
Ramírez
E
E
Hernández
A
A
Morales
E
E
Praga
M
M
Morales
J M
JM
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D011507:Proteinuria / Q000517:prevention & control*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone