Effect of losartan and amlodipine on proteinuria and transforming growth factor-beta1 in patients with IgA nephropathy.
BACKGROUND
Transforming growth factor-beta1 (TGF-beta1) is the major profibrotic cytokine involved in many renal diseases, and urinary TGF-beta1 reflects intrarenal TGF-beta1 production. Urinary TGF-beta1 excretion is reported to be significantly increased in patients with immunoglobulin A (IgA) nephropathy. The aim of the present study was to compare the effects of losartan and amlodipine on proteinuria, as well as on serum and urine TGF-beta1 levels in IgA nephropathy patients with hypertension and proteinuria.


METHODS
The initial 4 week washout period was followed by 12 weeks of active treatment, in which patients were randomized to once-daily treatment with losartan 50 mg (group 1, n=20) or amlodipine 5 mg (group 2, n=16). Urinary protein and TGF-beta1 excretion, serum TGF-beta1 and other clinical parameters were determined at baseline and during 12 weeks of active treatment.


RESULTS
Both treatments controlled blood pressure (BP) to a similar degree, and renal function and other biochemical parameters did not change during the study period. Urinary protein and TGF-beta1 excretions were significantly elevated in IgA nephropathy patients. Losartan significantly reduced urinary protein (from 2.3+/-1.5 g/day at baseline to 1.2+/-1.5 g/day at 12 weeks, P<0.05) and urinary TGF-beta1 excretion (from 31.2+/-14.0 pg/mg creatinine at baseline to 22.1+/-13.5 pg/mg creatinine at 12 weeks, P<0.05). In contrast, amlodipine had no affect on urinary protein and TGF-beta1 excretion. Both losartan and amlodipine failed to reduce serum TGF-beta1 levels.


CONCLUSIONS
Losartan and amlodipine, with similar control of BP, showed different effects on urine protein or TGF-beta1 excretion. Whereas losartan improved both urinary parameters, amlodipine did not. These differences might be important for the management of IgA nephropathy.
Department of Internal Medicine, College of Medicine, Institute of Kidney Disease, Yonsei University, Seoul, Korea.
Hyeong Cheon
HC
Park
Zhong Gao
ZG
Xu
Sorae
S
Choi
Young Suck
YS
Goo
Shin Wook
SW
Kang
Kyu Hun
KH
Choi
Sung Kyu
SK
Ha
Ho Yung
HY
Lee
Dae Suk
DS
Han
D000328:Adult; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects* / Q000652:urine; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome
D000959:Antihypertensive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017311:Amlodipine; D019808:Losartan