Clinical Trial: Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Renal Protective Effect of ACEI and ARB in Primary Hyperoxaluria

Brief Summary:

This study will test the effectiveness of two medications: ACEI (angiotensin converting enzyme inhibitor)and ARB (angiotensin receptor blocker) in reducing the renal injury induced by hyperoxaluria in patients with Primary Hyperoxaluria.

Hypothesis: Calcium oxalate crystal deposition in the kidney causes inflammation and resulting injury to kidney tissue. Angiotensin blockade will improve these changes, thus slowing the progression of renal insufficiency in patients with Primary Hyperoxaluria.

Detailed Summary:

In patients with primary hyperoxaluria (PH), deficiency of hepatic enzymes important in disposition of glyoxylate results in marked hyperoxaluria. Calcium oxalate crystals and high oxalate concentrations in the renal filtrate result in inflammation and injury in the renal parenchyma. Loss of renal function over time is characteristic, with end stage renal failure occurring in half the patients by age 35 years, but as early as infancy in some patients. Experience in animal models of hyperoxaluria, and from other renal diseases, supports a role for ACEI and ARB medications in ameliorating inflammation and injury thus providing a renal protective effect.

We propose to study the short-term effect of combined angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocking (ARB) therapy in patients with PH, in a controlled, randomized, two-year study. Primary endpoints will be urinary markers of renal tubular injury (retinol binding protein (RBP), alpha 1 microglobulin (α1m), γ-glutamyl transferase (GGT)) and interstitial fibrosis (transforming growth factor beta 1 (TGFβ1). Secondary endpoints will be the rates of change in renal tubular injury and renal function as determined by serum creatinine and creatinine clearance.

Sponsor: Mayo Clinic

Current Primary Outcome: Two-year change in the urinary markers of renal tubular injury and interstitial fibrosis [ Time Frame: 2 years ]

Original Primary Outcome: Study start:serum creatinine, electrolytes, chemistry profile, CBC, spot urine collection, two 24-hour urine collections. 6-month intervals over two years:Renal tubular markers,CaOx supersaturation,plasma renin,renal function,chem panel.

Current Secondary Outcome: Rate of change in 1. Renal tubular injury markers and 2. Renal function as determined by serum creatinine and creatinine clearance. [ Time Frame: 2 years ]

Original Secondary Outcome:

Information By: Mayo Clinic

Dates:
Date Received: January 19, 2006
Date Started: December 2007
Date Completion:
Last Updated: April 6, 2015
Last Verified: April 2015