Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-β levels

Rajiv Agarwal, Senthuran Siva, Stephen R. Dunn, Kumar Sharma

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Progression of renal failure, despite renoprotection with angiotensin-converting enzyme (ACE) inhibitors in patients with proteinuric nephropathies, may be caused by persistent renal production of transforming growth factor-β1 (TGF-β1) through the angiotensin II subtype I 1 (AT1) receptors. We tested the hypothesis that AT1-receptor blocker therapy added to a background of chronic maximal ACE inhibitor therapy will result in a reduction in urinary TGF-β1 levels in such patients. Sixteen patients completed a two-period, crossover, randomized, controlled trial, details of which have been previously reported. All patients were administered lisinopril, 40 mg/d, with either losartan, 50 mg/d, or placebo. Blood pressure (BP) was measured using a 24-hour ambulatory BP monitor. Overnight specimens of urine were analyzed for urine TGF-β1, protein, and creatinine concentrations. Mean age of the study population was 53 ± 9 (SD) years; body mass index, 38 ± 5.7 kg/m2; seated BP, 156 ± 18/88 ± 12 mm Hg; and urine protein excretion, 3.6 ± 0.71 g/g of creatinine. Twelve patients had diabetic nephropathy, and the remainder had chronic glomerulonephritis. At baseline, urinary TGF-β1 levels were significantly increased in the study population compared with healthy controls (13.2 ± 1.2 versus 1.7 ± 1.1 ng/g creatinine; P < 0.001). There was a strong correlation between baseline urine protein excretion and urinary TGF-β1 level (r2 = 0.53; P= 0.001), as well as systolic BP and urinary TGF-β1 level (r2 = 0.57; P < 0.001). After 4 weeks of add-on losartan therapy, there was a 38% (95% confidence interval [CI], 16% to 55%) decline in urinary TG F-β1 levels (13.3 [95% Cl, 11.4 to 15.5] to 8.2 pg/mg creatinine [95% Cl, 6.2 to 10.7]). The reduction in urinary TGF-β1 levels occurred independent of changes in mean urinary protein excretion or BP. Thus, proteinuric patients with renal failure, despite maximal ACE inhibition, had increased urinary levels of TGF-β1 that improved over 1 month of add-on therapy with losartan. We speculate that dual blockade with losartan and an ACE inhibitor may provide additional renoprotection by decreasing renal production of TGF-β1.

Original languageEnglish (US)
Pages (from-to)486-492
Number of pages7
JournalAmerican Journal of Kidney Diseases
Volume39
Issue number3
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Angiotensin Receptors
Transforming Growth Factors
Losartan
Blood Pressure
Creatinine
Angiotensin-Converting Enzyme Inhibitors
Urine
Renal Insufficiency
Proteins
Blood Pressure Monitors
Lisinopril
Enzyme Therapy
Kidney
Diabetic Nephropathies
Peptidyl-Dipeptidase A
Glomerulonephritis
Angiotensin II
Population
Body Mass Index
Therapeutics

Keywords

  • Ambulatory blood pressure (BP)
  • Anglotensin-converting enzyme (ACE) inhibitors
  • Chronic renal failure (CRF)
  • Losartan
  • Proteinuria
  • Transforming growth factor-β (TGF-β)

ASJC Scopus subject areas

  • Nephrology

Cite this

Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-β levels. / Agarwal, Rajiv; Siva, Senthuran; Dunn, Stephen R.; Sharma, Kumar.

In: American Journal of Kidney Diseases, Vol. 39, No. 3, 01.01.2002, p. 486-492.

Research output: Contribution to journalArticle

Agarwal, Rajiv ; Siva, Senthuran ; Dunn, Stephen R. ; Sharma, Kumar. / Add-on angiotensin II receptor blockade lowers urinary transforming growth factor-β levels. In: American Journal of Kidney Diseases. 2002 ; Vol. 39, No. 3. pp. 486-492.
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