Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-β, and nitrite excretion

Liora Adler,Clifford E Kashtan,Howard Trachtman,Bernard G Gauthier,Rachel Frank,Stephen Futterweit,Roy Mathew

doi:10.1186/1471-2369-3-2

Abstract

BackgroundAngiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate.Methods11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Patients were treated with enalapril, ≅ 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion.ResultsPrior to treatment, urinary excretion of transforming growth factor-β and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-β, or nitrite excretion.ConclusionThese findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-β and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted.

Highlights

Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects
Blood was not drawn at the end of the 14-day EN treatment period and, as a consequence, the effect of ACEl therapy on glomerular filtration rate (GFR) could not be determined
Male patients with Alport syndrome (AS) are at greater risk than females of developing progressive kidney failure, our findings suggest that differences in renal production of Transforming growth factor-β (TGF-β) in the early phase of the disease cannot explain the impact of gender on prognosis

Summary

Introduction

Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate. Alport syndrome (AS) is a glomerulopathy caused by genetic mutations in type IV collagen, the main collagenous constituent of the glomerular basement membrane (GBM) [1]. Hematuria is the initial finding and proteinuria develops later secondary to the defective composition and ultrastructure of the GBM [1]. Proteinuria increases with age and is a useful marker of disease progression. There is no specific therapy for AS and renal transplantation remains the definitive treatment [1]

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