Factors Influencing Oxalate Synthesis in Healthy Volunteers.

Urine oxalate excretion influences the risk of calcium oxalate kidney stone formation and has been reported to positively correlate with body mass index (BMI) and body weight. The two major sources of urine oxalate are dietary oxalate absorption and endogenous oxalate synthesis (EOS). In this study, we investigated the association between EOS, as estimated by oxalate content of 24-hour urine collected while consuming an ultra-low oxalate diet, and measures of body size and composition.

Hyperoxaluria: Diagnosis and Treatment.

Hyperoxaluria is categorized as either primary (PH), enteric (EH), or idiopathic (IH). The PHs are a group of ultra-rare genetic disorders resulting in oxalate overproduction that can result in end-stage renal disease (ESRD). Novel RNA inhibitory drugs are now available to treat PH that significantly reduced the risk of kidney stones.

Inducing Colonization Reduces Urinary Oxalate in Healthy Adults.

Introduction: Oxalate-degrading intestinal bacteria, including the oxalate-degrading specialist, have the potential to reduce urinary oxalate excretion in humans, and thus limit the risk of calcium oxalate kidney stone formation. The aim of this proof-of-concept study, which was performed in healthy adults, was to demonstrate that ingestion of live is safe, can establish sustainable gut colonization, and reduce urinary oxalate excretion.

Methods: Twenty-two healthy adults without a history of kidney stones and not colonized with ingested diets controlled in oxalate and calcium.

Eligibility of Living Kidney Donors with Kidney Stone Disease.

Introduction: Guidelines recommend that patients with a self-reported history of kidney stones or stones on imaging during living kidney donor (LKD) evaluation undergo 24-h urine stone risk testing. We examined eligibility decisions for LKD candidates at two high-volume academic transplant centers based on 24-h urine testing and imaging findings.

Methods: We identified potential LKDs with a self-reported history of kidney stones or stones identified on imaging, who underwent 24-h urine collection.

Metabolic dysfunction associated steatotic liver and kidney stones: what is going on?

Purpose Of Review: Metabolic dysfunction associated steatotic liver disease (MASLD) is increasing throughout the world, affecting nearly one in three individuals. Kidney stone disease, which is also increasing, is associated with MASLD. Common risk factors for both, including obesity, diabetes, dyslipidemia, hypertension, and metabolic syndrome, are likely drivers of this association.

The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria.

Purpose: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion.

4-hydroxy-2-oxoglutarate metabolism in a mouse model of Primary Hyperoxaluria Type 3.

Primary Hyperoxaluria Type 3 (PH3) results from 4-hydroxy-2-oxoglutarate (HOG) aldolase (HOGA) deficiency, which causes an increase in endogenous oxalate synthesis leading to calcium oxalate kidney stone disease. The mechanisms underlying HOG metabolism and increased oxalate synthesis in PH3 are not well understood. We used a knock-out mouse model of PH3 to investigate two aspects of HOG metabolism: reduction to dihydroxyglutarate (DHG), a pathway that may limit oxalate synthesis in PH3, and metabolism to glyoxylate, which is a direct precursor to oxalate.

End Point Considerations for Clinical Trials in Enteric Hyperoxaluria.

Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown.

Associations of Obesity and Neighborhood Factors With Urinary Stone Parameters.

Introduction: Obesity is associated with kidney stone disease, but it is unknown whether this association differs by SES. This study assessed the extent to which obesity and neighborhood characteristics jointly contribute to urinary risk factors for kidney stone disease.

Methods: This was a retrospective analysis of adult patients with kidney stone disease evaluated with 24-hour urine collection (2001-2020).

Primary hyperoxaluria type 1: time for prime time?

Oxalate crystals in the kidney were first described in 1925. Since then, many major milestones have been reached in the understanding of genetic primary hyperoxaluria(s). Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease due to a mutation in the gene, which encodes the hepatic peroxisomal enzyme alanine-glyoxylate aminotransferase (AGT), inducing excess oxalate production and further kidney stones, nephrocalcinosis and chronic kidney disease (CKD).

Generation of a GLO-2 deficient mouse reveals its effects on liver carbonyl and glutathione levels.

Objective: Hydroxyacylglutathione hydrolase (aka as GLO-2) is a component of the glyoxalase pathway involved in the detoxification of the reactive oxoaldehydes, glyoxal and methylglyoxal. These reactive metabolites have been linked to a variety of pathological conditions, including diabetes, cancer and heart disease and may be involved in the aging process. The objective of this study was to generate a mouse model deficient in GLO-2 to provide insight into the function of GLO-2 and to determine if it is potentially linked to endogenous oxalate synthesis which could influence urinary oxalate excretion.

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.

Disparities in Kidney Stone Disease: A Scoping Review.

Purpose: We reviewed the available evidence regarding health disparities in kidney stone disease to identify knowledge gaps in this area.

Materials And Methods: A literature search was conducted using PubMed®, Embase® and Scopus® limited to articles published in English from 1971 to 2020. Articles were selected based on their relevance to disparities in kidney stone disease among adults in the United States.

Effect of alanine supplementation on oxalate synthesis.

The Primary Hyperoxalurias (PH) are rare disorders of metabolism leading to excessive endogenous synthesis of oxalate and recurring calcium oxalate kidney stones. Alanine glyoxylate aminotransferase (AGT), deficient in PH type 1, is a key enzyme in limiting glyoxylate oxidation to oxalate. The affinity of AGT for its co-substrate, alanine, is low suggesting that its metabolic activity could be sub-optimal in vivo.

Screening for primary hyperparathyroidism in a tertiary stone clinic, a useful endeavor.

Introduction And Objectives: Primary hyperparathyroidism (1HPT) is associated with the risk of developing kidney stones. Our objective was to determine the prevalence of 1HPT amongst SF evaluated at a tertiary stone clinic and determine if it is cost-effective to screen for this condition.

Methods: We retrospectively reviewed 742 adult SF seen by a single urologic surgeon from 2012 to 2017 all of who were screened for 1HPT with an intact serum PTH (iPTH) and calcium.

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.