Clinical Trial: Enalapril in Collagen Type 4 Nephropathy

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Collagen Type 4-related Nephropathies: From Alport to Thin Membrane Nephropathy. A Series of Cases Treated With Angiotensin Converting Enzyme Inhibitor

Brief Summary: Background: Collagen IV-related nephropathies can lead to End Stage Renal Disease. Experimental studies have shown renin angiotensin aldosterone system blockade can reduce proteinuria and preserve renal function. In humans there is no proven treatment. Methods: This is a retrospective study of patients with Collagen IV-related nephropathies and proteinuria treated with enalapril analyzing the evolution of proteinuria and renal function, as well as predictive variables of progression to end stage renal disease. Outcome was creatinine clearance < 60 ml/min/1.73m2.

Detailed Summary:

Introduction Collagen IV-related nephropathies, caused by mutations in the three genes encoding collagen type IV of the basal membrane, represent a spectrum of phenotypes from Alport syndrome (AS) to thin basement membrane nephropathy (TBMN) (1). Subtypes are X-linked AS (XLAS) which corresponds approximately 80% of AS, autosomal recessive AS (ARAS), counting for 15% of AS, and the autosomal dominant forms, represented by autosomal dominant AS (ADAS, 5% of AS) and TBMN, which is believed to be present in 1% of the population (1).

Besides renal manifestations, these diseases can present cochlear and ocular abnormalities (2). However, the hallmark of Collagen IV-related nephropathies is hematuria. Proteinuria is detected during life, being a marker of disease progression. All males with XLAS develop proteinuria and, eventually, progressive renal insufficiency, which leads to end-stage renal disease (ESRD). Overall, an estimated 60% reach ESRD by age 30 years, and 90% by age 40 years (2). Approximately 12% of females with XLAS develop ESRD before age 40 years, increasing to 30% by age 60 years (3). Most individuals with ARAS develop significant proteinuria in late childhood or adolescence and ESRD before age 30 years. Progression to ESRD is slower in individuals with ADAS. Similarly, TBMN is characterized clinically by persistent microhematuria often observed in childhood. TBMN is rarely associated with extrarenal abnormalities and proteinuria. Hypertension and progression to ESRD are unusual (4).

Despite the severity of disease, the high rate of ESRD, and the increasing knowledge about genetics and diagnosis, there is currently no proven treatment to AS. So far, the therapeutic approach is limited to angiotensin-II (AII) blockade, blood pressure control and diet counseling. Angiotensin-converting enzyme inhibitors (ACEi) or
Sponsor: University of Sao Paulo

Current Primary Outcome: proteinuria [ Time Frame: two years ]

evaluate the proteinuria during two years of treatment with enalapril


Original Primary Outcome: Same as current

Current Secondary Outcome: evaluate the creatinine clearance during treatment with enalapril [ Time Frame: two years ]

Original Secondary Outcome: Same as current

Information By: University of Sao Paulo

Dates:
Date Received: October 27, 2011
Date Started: January 2011
Date Completion:
Last Updated: November 1, 2011
Last Verified: November 2011