Forty Years of Oxalobacter formigenes, a Gutsy Oxalate-Degrading Specialist.

Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism and the lack of studies which have utilized diets in which the oxalate content is controlled.

Dietary Oxalate Induces Urinary Nanocrystals in Humans.

Introduction: Crystalluria is thought to be associated with kidney stone formation and can occur when urine becomes supersaturated with calcium, oxalate, and phosphate. The principal method used to identify urinary crystals is microscopy, with or without a polarized light source. This method can detect crystals above 1 μm in diameter (microcrystals).

Future treatments for hyperoxaluria.

Purpose Of Review: The review of potential therapies in the treatment of hyperoxaluria is timely, given the current excitement with clinical trials and the mounting evidence of the importance of oxalate in both kidney stone and chronic kidney disease.

Recent Findings: Given the significant contribution of both endogenous and dietary oxalate to urinary oxalate excretions, it is not surprising therapeutic targets are being studied in both pathways. This article covers the existing data on endogenous and dietary oxalate and the current targets in these pathways.

The effects of the inactivation of Hydroxyproline dehydrogenase on urinary oxalate and glycolate excretion in mouse models of primary hyperoxaluria.

The major clinical manifestation of the Primary Hyperoxalurias (PH) is increased production of oxalate, as a consequence of genetic mutations that lead to aberrant glyoxylate and hydroxyproline metabolism. Hyperoxaluria can lead to the formation of calcium-oxalate kidney stones, nephrocalcinosis and renal failure. Current therapeutic approaches rely on organ transplants and more recently modifying the pathway of oxalate synthesis using siRNA therapy.

Crystal deposition triggers tubule dilation that accelerates cystogenesis in polycystic kidney disease.

The rate of disease progression in autosomal-dominant (AD) polycystic kidney disease (PKD) exhibits high intra-familial variability suggesting that environmental factors may play a role. We hypothesized that a prevalent form of renal insult may accelerate cystic progression and investigated tubular crystal deposition. We report that calcium oxalate (CaOx) crystal deposition led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tubule segments along the affected nephrons.

An Intervention to Increase 24-Hour Urine Collection Compliance.

Introduction: Compliance with 24-hour urine collections for assessing kidney stone risk is important in assigning preventive therapy. We determined factors associated with compliance and the impact of an intervention.

Methods: In 2015 those patients requiring 24-hour urine testing were instructed to contact the vendor (Litholink®) and were given instructions by the same nurse to arrange for collections.

Dietary oxalate and kidney stone formation.

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.

Accuracy in 24-hour Urine Collection at a Tertiary Center.

There is a paucity of studies addressing the accuracy of 24-hour urine collection for assessing stone risk parameters. Collection accuracy is thought to be essential for assigning optimal therapy for stone prevention. The objective of this study was to determine factors associated with accurate and inaccurate collections.

Oxalate induces mitochondrial dysfunction and disrupts redox homeostasis in a human monocyte derived cell line.

Monocytes/macrophages are thought to be recruited to the renal interstitium during calcium oxalate (CaOx) kidney stone disease for crystal clearance. Mitochondria play an important role in monocyte function during the immune response. We recently determined that monocytes in patients with CaOx kidney stones have decreased mitochondrial function compared to healthy subjects.

The L530R variation associated with recurrent kidney stones impairs the structure and function of TRPV5.

TRPV5 is a Ca-selective channel that plays a key role in the reabsorption of Ca ions in the kidney. Recently, a rare L530R variation (rs757494578) of TRPV5 was found to be associated with recurrent kidney stones in a founder population. However, it was unclear to what extent this variation alters the structure and function of TRPV5.

Dynamics of PVY strains in field grown potato: Impact of strain competition and ability to overcome host resistance mechanisms.

Potato virus Y (PVY) is the most important viral pathogen affecting potato crops worldwide. PVY can be transmitted non-persistently by aphids that do not colonize the host plant, resulting in a rapid acquisition and transmission of the virus between plants. PVY exists as a complex of strains that can be distinguished according to their pathogenicity, serology and genomic analysis.

RNA interference in the treatment of renal stone disease: Current status and future potentials.

Recent advances in RNA interference (RNAi) delivery and chemistry have resulted in the development of more than 20 RNAi-based therapeutics, several of which are now in Phase III trials. The most advanced clinical trials have utilized modifications such as lipid nanoparticles and conjugation to N-acetyl galactosamine to treat liver specific diseases. Recent reports have suggested that reducing endogenous oxalate synthesis by RNAi may be a safe and effective therapy for patients with the rare disease, Primary Hyperoxaluria (PH).

An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria.

Primary hyperoxaluria type 1 (PH1), an inherited rare disease of glyoxylate metabolism, arises from mutations in the enzyme alanine-glyoxylate aminotransferase. The resulting deficiency in this enzyme leads to abnormally high oxalate production resulting in calcium oxalate crystal formation and deposition in the kidney and many other tissues, with systemic oxalosis and ESRD being a common outcome. Although a small subset of patients manages the disease with vitamin B6 treatments, the only effective treatment for most is a combined liver-kidney transplant, which requires life-long immune suppression and carries significant mortality risk.

Ascorbic acid intake and oxalate synthesis.

In humans, approximately 60 mg of ascorbic acid (AA) breaks down in the body each day and has to be replaced by a dietary intake of 70 mg in women and 90 mg in men to maintain optimal health and AA homeostasis. The breakdown of AA is non-enzymatic and results in oxalate formation. The exact amount of oxalate formed has been difficult to ascertain primarily due to the limited availability of healthy human tissue for such research and the difficulty in measuring AA and its breakdown products.

Monocyte Mitochondrial Function in Calcium Oxalate Stone Formers.

Objective: To investigate whether mitochondrial function is altered in circulating immune cells from calcium oxalate (CaOx) stone formers compared to healthy subjects.

Materials And Methods: Adult healthy subjects (n = 18) and CaOx stone formers (n = 12) were included in a pilot study. Data collection included demographic and clinical values from electronic medical records.

Oxalate Concentrations in Human Gastrointestinal Fluid.

Background And Purpose: Urinary oxalate excretion is a risk factor for nephrolithiasis and is a result of endogenous metabolism and gastrointestinal processes. Gastrointestinal absorption of oxalate has been well demonstrated but to our knowledge evidence for secretion of oxalate is absent in humans. The objective of this study was to measure the amount and conformation of oxalate in the stomach and small intestine of adult subjects undergoing gastrointestinal endoscopy.

Proteome Dynamics of the Specialist Oxalate Degrader .

is a unique intestinal organism that relies on oxalate degradation to meet most of its energy and carbon needs. A lack of colonization is a risk factor for calcium oxalate kidney stone disease. The release of the genome sequence of has provided an opportunity to increase our understanding of the biology of .

Effects of alanine:glyoxylate aminotransferase variants and pyridoxine sensitivity on oxalate metabolism in a cell-based cytotoxicity assay.

The hereditary kidney stone disease primary hyperoxaluria type 1 (PH1) is caused by a functional deficiency of the liver-specific, peroxisomal, pyridoxal-phosphate-dependent enzyme, alanine:glyoxylate aminotransferase (AGT). One third of PH1 patients, particularly those expressing the p.[(Pro11Leu; Gly170Arg; Ile340Met)] mutant allele, respond clinically to pharmacological doses of pyridoxine.

Molecular Modeling of the Structural and Dynamical Changes in Calcium Channel TRPV5 Induced by the African-Specific A563T Variation.

Transient receptor potential cation channels, vanilloid subfamily, member 5 (TRPV5) plays a key role in active Ca(2+) reabsorption in the kidney. Variations in TRPV5 occur at high frequency in African populations and may contribute to their higher efficiency of Ca(2+) reabsorption. One of the African specific variations, A563T, exhibits increased Ca(2+) transport ability.