Pathological regression by angiotensin II type 1 receptor blockade in patients with mesangial proliferative glomerulonephritis.
Although angiotensin II type 1 receptor blocker (ARB) therapy reduces proteinuria and retards the progression of renal injury in patients with glomerulonephritis, whether these drugs actually ameliorate pathological damages in human glomerulonephritis has not been determined. Fifteen patients with biopsy-proven mild-to-moderate mesangial proliferative glomerulonephritis (10 with immunoglobulin A [IgA] nephropathy and 5 with non-IgA mesangial proliferative glomerulonephritis) received ARB monotherapy. In these patients, repeated renal biopsy was performed after a mean of 28.1 months, and pathological changes (including the mesangial matrix expansion ratio and interstitial fibrosis expansion ratio) were quantitatively examined using an image analyzer. Clinical markers were also evaluated, including the serum creatinine, serum IgA, creatinine clearance (Ccr), 24-h urinary protein excretion, urinary N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure. ARB therapy significantly reduced urinary protein excretion (0.68+/-0.63 to 0.20+/-0.32 g/day, p=0.016) and the blood pressure (systolic: 133.3+/-18.2 to 123.4+/-10.5 mmHg, p=0.041; diastolic: 79.4+/-11.9 to 72.0+/-8.2 mmHg, p=0.038). Although the global glomerular sclerosis ratio was unchanged (6.3+/-8.5% to 10.7+/-16.1%, p=0.33), the mesangial matrix expansion ratio (33.1+/-10.8% to 22.7+/-7.8%, p=0.001) and the interstitial fibrosis ratio (19.9+/-5.8% to 13.8+/-4.4%, p=0.034) were significantly reduced by ARB treatment. The levels of pathological improvement were similar between patients with IgA nephropathy and those with non-IgA mesangial proliferative glomerulonephritis. The results of the present study strongly suggest that ARB monotherapy can significantly reverse pathological changes, including mesangial matrix expansion and interstitial fibrosis, in human glomerulonephritis.
Ohtake
Takayasu
T
Department of Nephrology, and Kidney and Dialysis Center, Shonan Kamakura General Hospital, Kamakura, Japan. ohtake@shonankamakura.or.jp
Oka
Machiko
M
Maesato
Kyoko
K
Mano
Tsutomu
T
Ikee
Ryota
R
Moriya
Hidekazu
H
Kobayashi
Shuzo
S
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D044140:Receptor, Angiotensin, Type 1; D012189:Retrospective Studies; D000077333:Telmisartan; D013777:Tetrazoles / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan; D014664:Vasodilation
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007070:Immunoglobulin A; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068756:Valsartan; D003404:Creatinine; D014633:Valine; D019808:Losartan; D000077333:Telmisartan