The effect of aldosterone blockade in patients with Alport syndrome.
Recent studies indicate that adding the mineralocorticoid receptor antagonist spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI and angiotensin receptor blocker (ARB), which is known as a triple blockade, enhances the more beneficial effects on urinary protein excretion of patients with chronic kidney diseases. In this study, we explored the effects of SP on urinary protein excretion in patients with Alport syndrome featuring persistent proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and ARB (candesartan). Five patients with Alport syndrome were enrolled and SP treatment (25 mg/day) was started. At the start of SP administration, all patients showed good renal function and none of them suffered from hypertension. We decided to assess the effect of SP by determining the morning urinary protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR). After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and 18 months, while EGFR did not change. The drop in systolic and diastolic blood pressure was statistically significant and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l). These results suggest that aldosterone receptor blockade combined with ACEI and ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome as in those with other chronic kidney diseases. SP can thus be expected to constitute a good renoprotective agent for Alport syndrome. These preliminary data indicate that large-scale trials of this therapy should be done.
Kaito
Hiroshi
H
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan.
Nozu
Kandai
K
Iijima
Kazumoto
K
Nakanishi
Koichi
K
Yoshiya
Kunihiko
K
Kanda
Kyoko
K
Przybyslaw Krol
Rafal
R
Yoshikawa
Norishige
N
Matsuo
Masafumi
M
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D002648:Child; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009394:Nephritis, Hereditary / Q000188:drug therapy* / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy; D013148:Spironolactone / Q000494:pharmacology*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone