scholarly journals A Double-Blind, Placebo Controlled, Randomized Phase 1 Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme

2016 ◽  
Vol 44 (2) ◽  
pp. 150-158 ◽  
Author(s):  
Craig B. Langman ◽  
Danica Grujic ◽  
Rita M. Pease ◽  
Linda Easter ◽  
Jennifer Nezzer ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Healthy Volunteers ◽  
Treatment Period ◽  
Phase 1 ◽  
Urinary Oxalate ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Oxalate Excretion ◽  
Urinary Oxalate Excretion ◽  
Dietary Oxalate

Background: Hyperoxaluria may result from increased endogenous production or overabsorption of dietary oxalate in the gastrointestinal tract leading to nephrolithiasis and, in some, to oxalate nephropathy and chronic kidney disease. ALLN-177 is an oral formulation of a recombinant, oxalate specific, microbial enzyme oxalate decarboxylase intended to treat secondary hyperoxaluria by degrading dietary oxalate in the gastrointestinal tract, thereby reducing its absorption and subsequent excretion in the urine. Methods: This double-blind, placebo controlled, randomized, cross-over, phase 1 study of ALLN-177 evaluated the tolerability of ALLN-177 and its effect on urinary oxalate excretion in 30 healthy volunteers with hyperoxaluria induced by ingestion of a high oxalate, low calcium (HOLC) diet. The primary end point was the difference in the mean 24-hour urinary oxalate excretion during the ALLN-177 treatment period compared with the placebo treatment period. Results: The daily urinary oxalate excretion increased in the study population from 27.2 ± 9.5 mg/day during screening to 80.8 ± 24.1 mg/day (mean ± SD) on the HOLC diet before introducing ALLN-177 or placebo therapy for 7 days. Compared to placebo, ALLN-177 treatment reduced urinary oxalate by 11.6 ± 2.7 mg/day, p = 0.0002 (least squares mean ± SD). Conclusions: In healthy volunteers, with diet-induced hyperoxaluria treatment with ALLN-177, when compared to placebo, significantly reduced urinary oxalate excretion by degrading dietary oxalate in the gastrointestinal tract and thereby reducing its absorption. ALLN-177 may represent a new approach for managing secondary hyperoxaluria and its complications.

The effect of dietary hydroxyproline and dietary oxalate on urinary oxalate excretion in cats

2013 ◽  
Author(s):  
J. C. Dijcker ◽  
E. A. Hagen-Plantinga ◽  
D. G. Thomas ◽  
Y. Queau ◽  
V. Biourge ◽  
...  
Keyword(s):  
Urinary Oxalate ◽  
Oxalate Excretion ◽  
Urinary Oxalate Excretion ◽  
Dietary Oxalate

scholarly journals Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model

2015 ◽  
Vol 81 (15) ◽  
pp. 5048-5054 ◽  
Author(s):  
Xingsheng Li ◽  
Melissa L. Ellis ◽  
John Knight
Keyword(s):  
Kidney Stones ◽  
Host Bacterium ◽  
Urinary Oxalate ◽  
Oxalobacter Formigenes ◽  
Content Type ◽  
Oxalate Excretion ◽  
Urinary Oxalate Excretion ◽  
Dietary Oxalate ◽  
Different Levels ◽  
Unique Ability

ABSTRACTAnimal and human studies have provided compelling evidence that colonization of the intestine withOxalobacter formigenesreduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability ofO. formigenesto rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice withO. formigenesOxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate onO. formigenesintestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized withO. formigenesdemonstrated the highly efficient degradation of soluble oxalate byO. formigenesrelative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retainedO. formigenescolonization after a 1-week dietary oxalate deprivation. Animals not colonized withO. formigenesexcreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival ofO. formigenesduring periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions betweenO. formigenesand the host and factors that impact colonization.

scholarly journals Dietary oxalate and kidney stone formation

2019 ◽  
Vol 316 (3) ◽  
pp. F409-F413 ◽  
Author(s):  
Tanecia Mitchell ◽  
Parveen Kumar ◽  
Thanmaya Reddy ◽  
Kyle D. Wood ◽  
John Knight ◽  
...  
Keyword(s):  
Calcium Oxalate ◽  
Stone Formation ◽  
Continuous Variable ◽  
Urinary Oxalate ◽  
Calcium Oxalate Stone ◽  
Oxalate Excretion ◽  
Urinary Oxalate Excretion ◽  
Stone Growth ◽  
The Impact ◽  
Dietary Oxalate

Dietary oxalate is plant-derived and may be a component of vegetables, nuts, fruits, and grains. In normal individuals, approximately half of urinary oxalate is derived from the diet and half from endogenous synthesis. The amount of oxalate excreted in urine plays an important role in calcium oxalate stone formation. Large epidemiological cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, individuals with oxalate excretions >25 mg/day may benefit from a reduction of urinary oxalate output. The 24-h urine assessment may miss periods of transient surges in urinary oxalate excretion, which may promote stone growth and is a limitation of this analysis. In this review we describe the impact of dietary oxalate and its contribution to stone growth. To limit calcium oxalate stone growth, we advocate that patients maintain appropriate hydration, avoid oxalate-rich foods, and consume an adequate amount of calcium.

The effect of dietary hydroxyproline and dietary oxalate on urinary oxalate excretion in cats1

2014 ◽  
Vol 92 (2) ◽  
pp. 577-584 ◽  
Author(s):  
J. C. Dijcker ◽  
E. A. Hagen-Plantinga ◽  
D. G. Thomas ◽  
Y. Queau ◽  
V. Biourge ◽  
...  
Keyword(s):  
Urinary Oxalate ◽  
Oxalate Excretion ◽  
Urinary Oxalate Excretion ◽  
Dietary Oxalate
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