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.

Plant-Based Milk Alternatives and Risk Factors for Kidney Stones and Chronic Kidney Disease.

Objective: Patients with kidney stones are counseled to eat a diet low in animal protein, sodium, and oxalate and rich in fruits and vegetables, with a modest amount of calcium, usually from dairy products. Restriction of sodium, potassium, and oxalate may also be recommended in patients with chronic kidney disease. Recently, plant-based diets have gained popularity owing to health, environmental, and animal welfare considerations.

Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion.

Kidney stone disease is increasing in prevalence, and the most common stone composition is calcium oxalate. Dietary oxalate intake and endogenous production of oxalate are important in the pathophysiology of calcium oxalate stone disease. The impact of dietary oxalate intake on urinary oxalate excretion and kidney stone disease risk has been assessed through large cohort studies as well as smaller studies with dietary control.

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).

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.

Reduction in urinary oxalate excretion in mouse models of Primary Hyperoxaluria by RNA interference inhibition of liver lactate dehydrogenase activity.

The Primary Hyperoxaluria's (PH) are rare autosomal recessive disorders characterized by elevated oxalate production. PH patients suffer recurrent calcium oxalate kidney stone disease, and in severe cases end stage renal disease. Recent evidence has shown that RNA interference may be a suitable approach to reduce oxalate production in PH patients by knocking down key enzymes involved in hepatic oxalate synthesis.

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.

Modeling the structural and dynamical changes of the epithelial calcium channel TRPV5 caused by the A563T variation based on the structure of TRPV6.

TRPV5, transient receptor potential cation channel vanilloid subfamily member 5, is an epithelial Ca channel that plays a key role in the active Ca reabsorption process in the kidney. A single nucleotide polymorphism (SNP) rs4252499 in the TRPV5 gene results in an A563T variation in the sixth transmembrane (TM) domain of TRPV5. Our previous study indicated that this variation increases the Ca transport function of TRPV5.

Hydroxyproline Metabolism and Oxalate Synthesis in Primary Hyperoxaluria.

Endogenous oxalate synthesis contributes to calcium oxalate stone disease and is markedly increased in the inherited primary hyperoxaluria (PH) disorders. The incomplete knowledge regarding oxalate synthesis complicates discovery of new treatments. Hydroxyproline (Hyp) metabolism results in the formation of oxalate and glycolate.

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.

Steatorrhea and Hyperoxaluria in Severely Obese Patients Before and After Roux-en-Y Gastric Bypass.

Background And Aims: Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) is generally attributed to fat malabsorption. If hyperoxaluria is indeed caused by fat malabsorption, magnitudes of hyperoxaluria and steatorrhea should correlate. Severely obese patients, prior to bypass, ingest excess dietary fat that can produce hyperphagic steatorrhea.

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.

Metabolism of (13)C5-hydroxyproline in mouse models of Primary Hyperoxaluria and its inhibition by RNAi therapeutics targeting liver glycolate oxidase and hydroxyproline dehydrogenase.

Excessive endogenous oxalate synthesis can result in calcium oxalate kidney stone formation and renal failure. Hydroxyproline catabolism in the liver and kidney contributes to endogenous oxalate production in mammals. To quantify this contribution we have infused Wt mice, Agxt KO mice deficient in liver alanine:glyoxylate aminotransferase, and Grhpr KO mice deficient in glyoxylate reductase, with (13)C5-hydroxyproline.

Lowering urinary oxalate excretion to decrease calcium oxalate stone disease.

Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion.