Clinical Trial: Hydroxyproline Influence on Oxalate Metabolism
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: Influence of Hydroxyproline Plasma Concentration on Its Metabolism to Oxalate
Brief Summary:
Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues.
Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a signficant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease.
This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow us to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.
Detailed Summary:
The purpose of this study is to determine the contribution of hydroxyproline metabolism to urinary oxalate and glycolate excretion in patients with primary hyperoxaluria.
Oxalic acid (COOH)2 is an end product of metabolism that is synthesized mainly in the liver. We have estimated that 10 - 20 mg is synthesized in the body of healthy adults each day (1). The main precursor of oxalate is glyoxylate (CHO•COOH). The bulk of the glyoxylate formed is normally transaminated to glycine (NH2•CH2•COOH) by alanine: lyoxylate aminotransferase (AGT) or reduced to glycolate (CHOH•COOH) by glyoxylate reductase (GR). Less than 10% of the glyoxylate is oxidized to oxalate by lactate dehydrogenase (LDH). In individuals with the disease, primary hyperoxaluria, AGT, GR, or HOGA enzyme is deficient and the amount of oxalate synthesized by the liver increases to 80 - 300 mg per day. The increased oxalate excreted in urine can cause damage to kidney tissue. Calcium oxalate stones may form in the kidney or calcium oxalate crystals may deposit in renal tubules and the renal parenchyma (nephrocalcinosis). An increased rate of oxalate synthesis could also contribute to idiopathic calcium oxalate stone disease. Understanding the pathways of endogenous oxalate synthesis and identifying strategies that decrease oxalate production could be beneficial for individuals with these diseases.
Hydroxyproline is the primary source of glyoxylate identified in the body (2). Daily collagen turnover of bone results in the formation of 300 - 450 mg of hydroxyproline, which cannot be re-utilized by the body and is broken down. This metabolism yields 180 - 250 mg of glyoxylate. Further hydroxyproline is obtained from the diet, primarily from meat and gelatin-containing products. The bulk of the glyoxylate formed is converted to glycine by the
Sponsor: Mayo Clinic
Current Primary Outcome: The mean percent conversion of hydroxyproline to urinary oxalate [ Time Frame: Participants will be followed for the duration of study infusion and observation, an average of 24 hours. ]
Original Primary Outcome: Same as current
Current Secondary Outcome: The mean percent conversion of hydroxyproline to urinary glycolate [ Time Frame: Participants will be followed for the duration of the study infusion and observations, an average of 24 hours. ]
Original Secondary Outcome: Same as current
Information By: Mayo Clinic
Dates:
Date Received: December 19, 2013
Date Started: September 2013
Date Completion: January 2017
Last Updated: July 5, 2016
Last Verified: July 2016
