Oxalate Load Research Articles

Impact of Sprouting on the Oxalate Load of Proteinaceous Plant Based Foods

Total oxalate content of plant-based foods has a prominent impact on renal calculi formation in animals and man. The present study was aimed to estimate total oxalate in six selected whole dry seed samples namely Chick pea - Cicer arietinum (S1), Red cowpea – Vigna unguiculata (S2), Green pea – Pisum sativum (S3), Mung bean – Vigna radiata (S4), Almond- Prunus dulcis (S5) and Soybean – Glycine max (S6) and their seed coats used as protein rich foods at 0 hrs., 24 hrs. And 48 hrs. Post soaking in distilled water. Total oxalate (TO) levels were found to be decreased in all the sprouted whole seeds at 24 hrs. And 48 hrs. Than 0 hrs. Post soaking. Whole seeds of S2 contained maximum TO (400mg/100g sample) prior to sprouting which on soaking for 48 hrs. Reduced TO (122mg/100g). Maximum reduction in TO after 48 hrs. Was in S4 (292mg-25mg/100g). S1, S3, S5 and S6 exhibited lowering of TO by (243mg-80mg, 93mg-35mg, 343mg-133mg, 232mg-85mg per 100g sample) respectively. Sprouting induced more than 60% reduction of TO in whole seeds. Seed coat analysis of S4 (259mg-404mg/100g sample) and S5 (280mg-134mg/100g sample) projected an increase in TO post 24 hrs. Soaking, but further soaking till 48 hrs. Decreased the oxalate load to 261 mg and102 mg respectively. Seed coats of S1 and S3 shows lowering of TO from 30mg/100g sample and 33mg/100g sample to12mg/100g and 13 mg/100gsample. Sprouting, regulated oxalate levels in plant-based foods and exclusion of seed coats could reduce oxalate intake. Total Oxalate analysis of plant-based foods need to be addressed for safety of renal patients in choosing low oxalate diet.

Oxalate disrupts monocyte and macrophage cellular function via Interleukin-10 and mitochondrial reactive oxygen species (ROS) signaling

Oxalate is a small compound found in certain plant-derived foods and is a major component of calcium oxalate (CaOx) kidney stones. Individuals that consume oxalate enriched meals have an increased risk of forming urinary crystals, which are precursors to CaOx kidney stones. We previously reported that a single dietary oxalate load induces nanocrystalluria and reduces monocyte cellular bioenergetics in healthy adults. The purpose of this study was to extend these investigations to identify specific oxalate-mediated mechanisms in monocytes and macrophages. We performed RNA-Sequencing analysis on monocytes isolated from healthy subjects exposed to a high oxalate (8 mmol) dietary load. RNA-sequencing revealed 1,198 genes were altered and Ingenuity Pathway Analysis demonstrated modifications in several pathways including Interleukin-10 (IL-10) anti-inflammatory cytokine signaling, mitochondrial metabolism and function, oxalic acid downstream signaling, and autophagy. Based on these findings, we hypothesized that oxalate induces mitochondrial and lysosomal dysfunction in monocytes and macrophages via IL-10 and reactive oxygen species (ROS) signaling which can be reversed with exogenous IL-10 or Mitoquinone (MitoQ; a mitochondrial targeted antioxidant). We exposed monocytes and macrophages to oxalate in an in-vitro setting which caused oxidative stress, a decline in IL-10 cytokine levels, mitochondrial and lysosomal dysfunction, and impaired autophagy in both cell types. Administration of exogenous IL-10 and MitoQ attenuated these responses. These findings suggest that oxalate impairs metabolism and immune response via IL-10 signaling and mitochondrial ROS generation in both monocytes and macrophages which can be potentially limited or reversed. Future studies will examine the benefits of these therapies on CaOx crystal formation and growth in vivo.

Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats.

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.

MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA

You have accessJournal of UrologyCME1 Apr 2023MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA William DeFoor, Joonsue Lee, Nehus Edward, Marion Schulte, Sydney Huesman, Ashleigh Libs, and Prasad Devarajan William DeFoorWilliam DeFoor More articles by this author , Joonsue LeeJoonsue Lee More articles by this author , Nehus EdwardNehus Edward More articles by this author , Marion SchulteMarion Schulte More articles by this author , Sydney HuesmanSydney Huesman More articles by this author , Ashleigh LibsAshleigh Libs More articles by this author , and Prasad DevarajanPrasad Devarajan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medically complex, gastrostomy-fed children are particularly vulnerable to forming kidney stones. We have previously shown that there are elevated urinary oxalate levels in patients using enteral feeding formulas primarily based on soy protein, a known high oxalate food. Enteric hyperoxaluria may predispose patients to calcium oxalate stones. The objective of this study is assess if targeted dietary intervention decreases urinary oxalate excretion. METHODS: A retrospective cohort study was performed on medically complex children with cerebral palsy and severe developmental delay presenting to a high-volume Pediatric Stone Center with nephrolithiasis from 2015 to 2020. Inclusion criteria included those who underwent a dietary and urinary metabolic evaluation before and after the index visit. Diets were analyzed by a registered dietitian. Urinary metabolites including calcium, oxalate, and citrate as well as the supersaturations of calcium oxalate and calcium phosphate were analyzed via two 24-hour urine collections. Dietary oxalate load was determined by evaluating individual recipes for known high oxalate ingredients or soy-based formulas. Patients were stratified into those on a low versus high oxalate diet. Statistical analysis was performed using paired t-tests. RESULTS: A total of 13 medically complex stone-forming children met inclusion criteria. All patients were non-ambulatory. 11 of 13 (85%) were primarily fed via gastrostomy. Of the 13 patients, 4 were on a low oxalate diet and 9 were found to have a diet of high oxalate foods. The baseline urinary oxalate excretion (26 vs. 71 mg/m2/day, P = 0.001) and supersaturation of calcium oxalate (6.1 vs. 14.3, P=0.01) were lower in those with a low oxalate diet. Four patients on high oxalate diets were targeted for lowering the enteral oxalate load. A follow-up urinary metabolic evaluation was performed a mean of 6.5 months after the dietary intervention. The urinary oxalate level decreased from 71 to 33 mg/m2/day (P=0.049). Urinary excretion of calcium and citrate as well as the supersaturation of calcium phosphate were similar following dietary modifications. CONCLUSIONS: Urinary oxalate excretion and supersaturation of calcium oxalate were elevated in medically complex stone-forming children with high dietary oxalate content. Targeted dietary intervention to reduce the oxalate load in enteral formulas can lead to a substantial decrease in urinary oxalate excretion. Further investigation is required to determine if this leads to lower stone recurrence, hospitalizations, and the need for surgical interventions. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William DeFoor More articles by this author Joonsue Lee More articles by this author Nehus Edward More articles by this author Marion Schulte More articles by this author Sydney Huesman More articles by this author Ashleigh Libs More articles by this author Prasad Devarajan More articles by this author Expand All Advertisement PDF downloadLoading ...

Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis.

Nephrolithiasis is a common and recurrent disease affecting 9% of the US population. Hyperoxaluria is major risk factor for calcium oxalate kidney stones, which constitute two-thirds of all kidney stones. SLC26A3 (DRA, downregulated in adenoma) is an anion exchanger of chloride, bicarbonate, and oxalate thought to facilitate intestinal oxalate absorption, as evidenced by approximately 70% reduced urine oxalate excretion in knockout mice. We previously identified a small-molecule SLC26A3 inhibitor (DRAinh-A270) that selectively inhibited SLC26A3-mediated chloride/bicarbonate exchange (IC50 ~ 35 nM) and, as found here, oxalate/chloride exchange (IC50 ~ 60 nM). In colonic closed loops in mice, luminal DRAinh-A270 inhibited oxalate absorption by 70%. Following oral sodium oxalate loading in mice, DRAinh-A270 largely prevented the 2.5-fold increase in urine oxalate/creatinine ratio. In a mouse model of oxalate nephropathy produced by a high-oxalate low-calcium diet, vehicle-treated mice developed marked hyperoxaluria with elevated serum creatinine, renal calcium oxalate crystal deposition, and renal injury, which were largely prevented by DRAinh-A270 (10 mg/kg twice daily). DRAinh-A270 administered over 7 days to healthy mice did not show significant toxicity. Our findings support a major role of SLC26A3 in intestinal oxalate absorption and suggest the therapeutic utility of SLC26A3 inhibition for treatment of hyperoxaluria and prevention of calcium oxalate nephrolithiasis.

Oxalate Induced Mitochondrial and Lysosomal Dysfunction in Myeloid Cells is Mediated by IL‐10 Signaling

Oxalate is a small molecule found in several foods and is excreted in the urine. Accumulation of oxalate in the kidney can lead to crystal and kidney stone formation. Oxalate crystals have been reported to stimulate inflammation and injure renal epithelial cells. However, the effect of CaOx crystals on monocytes and macrophages is not fully‐characterized. Studies from our laboratory have shown that oxalate reduces mitochondrial metabolism and induces oxidative stress in monocytes and macrophages. The purpose of this study was to investigate additional mechanisms of oxalate‐induced changes in myeloid cells. Healthy adults were recruited for these studies and asked to consume a controlled oxalate diet for three days followed by a high oxalate load. Circulating monocytes and plasma were collected from participants before and after the oxalate load. Monocytes were examined using RNA‐sequencing, and plasma cytokine levels were evaluated using ELISA. Human primary macrophages and THP‐1 differentiated macrophages were used to assess mitochondrial quality control and lysosomal function following 24‐hour oxalate exposure using qRT‐PCR, western blotting, and microscopy. Transcriptomics revealed that 1,197 genes were differentially expressed in circulating monocytes following the oxalate load. Genes related to mitochondrial respiration, mitochondrial membrane potential, mitochondrial dysfunction, and IL‐10 signaling (regulator of mitochondrial metabolism) were significantly modified by oxalate. IL‐10 plasma cytokine levels were also significantly reduced. Macrophages exposed to oxalate had an accumulation of dysfunctional mitochondria and reduced lysosomal integrity. The findings from these studies indicate IL‐10 signaling may play a role in regulating mitochondrial quality control and lysosomal function in myeloid cells in response to oxalate. Additional studies investigating the significance of IL‐10 signaling on myeloid cells during crystal and stone formation are warranted.

Abstract 12660: Novel Model of Oxalate Diet Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats

Background: Diet induced models of chronic kidney disease (CKD) may offer several advantages vs surgical models in terms of clinical relevance and animal welfare. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. Increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction and eventually CKD. Dahl-salt-sensitive rats (Dahl-S) are a common strain used to study for hypertensive renal disease however characterization of other diet induced models on this background would allow for comparative studies of CKD within the same strain. We hypothesized that Dahl-S rats on a low-salt, oxalate rich diet would have increased renal injury and will serve as a novel rat model to study CKD. Methods/Results: Ten week-old male Dahl-S rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks (n=6-8/group). Real-time PCR demonstrated increased expression of inflammatory marker IL-6 (235% vs SS-NC, p&lt;0.0001) and fibrotic marker Timp-1 metalloproteinase (142% vs SS-NC, p&lt;0.0001) in the renal cortex of SS-OX rat kidneys compared to SS-NC. Immunohistochemistry of kidney tissue demonstrated increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (275% vs SS-NC, p&lt;0.001). In addition, SS-OX rats displayed increased 24-hour urinary protein excretion (UPE) (97% vs SS-NC, p&lt;0.01) as well as significant elevations of plasma Cystatin C (135% vs SS-NC, p&lt;0.01). Furthermore, oxalate diet induced hypertension (23% increase in systolic blood pressure vs. SS-NC, p&lt;0.05) and renin-angiotensin-aldosterone system (RAAS) profiling (via LC-MS/MS) in the SS-OX plasma showed significant (p&lt;0.05) increases in angiotensin [1-5] (128% vs SS-NC) and angiotensin I (56% vs SS-NC) as well as suppression of the steroid aldosterone (-54% vs SS-NC). Conclusion: Oxalate diet induces significant renal inflammation, fibrosis, renal dysfunction, decreased aldosterone secretion as well as RAAS activation and hypertension in Dahl-S rats and provides a novel diet-induced model to study hypertension and CKD.

Dietary Oxalate Loading Impacts Monocyte Metabolism and Inflammatory Signaling in Humans.

Diet has been associated with several metabolic diseases and may impact immunity. Increased consumption of meals with high oxalate content may stimulate urinary calcium oxalate (CaOx) crystals, which are precursors to CaOx kidney stones. We previously reported that CaOx stone formers have decreased monocyte cellular bioenergetics compared to healthy participants and oxalate reduces monocyte metabolism and redox status in vitro. The purpose of this study was to investigate whether dietary oxalate loading impacts monocyte cellular bioenergetics, mitochondrial complex activity, and inflammatory signaling in humans. Healthy participants (n = 40; 31.1 ± 1.3 years) with a BMI of 24.9 ± 0.6 kg/m2 consumed a controlled low oxalate diet for 3 days before drinking a blended preparation of fruits and vegetables containing a large amount of oxalate. Blood and urine were collected before (pre-oxalate) and for 5 h after the oxalate load to assess urinary oxalate levels, monocyte cellular bioenergetics and mitochondrial complex activity, and plasma cytokine/chemokine levels. Urinary oxalate levels significantly increased in post-oxalate samples compared to pre-oxalate samples. Monocyte cellular bioenergetics, mitochondrial complex I activity, and plasma cytokine and chemokine levels were altered to varying degrees within the study cohort. We demonstrate for the first time that dietary oxalate loading may impact monocyte metabolism and immune response in a cohort of healthy adults, but these response are variable. Further studies are warranted to understand oxalate mediated mechanisms on circulating monocytes and how this potentially influences CaOx kidney stone formation.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03877276.

Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis.

Kidney stones are becoming more prevalent worldwide in adults and children. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Crystalluria occurs when urine becomes supersaturated with minerals (e.g., calcium, oxalate, phosphate) and precedes kidney stone formation. Standard methods to assess crystalluria in stone formers include microscopy, filtration, and centrifugation. However, these methods primarily detect microcrystals and not nanocrystals. Nanocrystals have been suggested to be more harmful to kidney epithelial cells than microcrystals in vitro. Here, we describe the ability of Nanoparticle Tracking analysis (NTA) to detect human urinary nanocrystals. Healthy adults were fed a controlled oxalate diet prior to drinking an oxalate load to stimulate urinary nanocrystals. Urine was collected for 24 hours before and after the oxalate load. Samples were processed and washed with ethanol to purify samples. Urinary nanocrystals were stained with the calcium binding fluorophore, Fluo-4 AM. After staining, the size and count of nanocrystals were determined using NTA. The findings from this study show NTA can efficiently detect nanocrystalluria in healthy adults. These findings suggest NTA could be a valuable early detection method of nanocrystalluria in patients with kidney stone disease.

Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease

Introduction: Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. Methods: A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE^−/− mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe Oxalobacter formigenes (O. formigenes) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). Results: Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The O. formigenes intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the O. formigenes group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. Conclusions: Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by O. formigenes might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD.

Dietary Oxalate Intake and Kidney Outcomes.

Oxalate is both a plant-derived molecule and a terminal toxic metabolite with no known physiological function in humans. It is predominantly eliminated by the kidneys through glomerular filtration and tubular secretion. Regardless of the cause, the increased load of dietary oxalate presented to the kidneys has been linked to different kidney-related conditions and injuries, including calcium oxalate nephrolithiasis, acute and chronic kidney disease. In this paper, we review the current literature on the association between dietary oxalate intake and kidney outcomes.

Dietary Oxalate Induces Urinary Nanocrystals in Humans

IntroductionCrystalluria 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). However, analyses of calcium oxalate kidney stones have indicated that crystallite components in these calculi are 50–100 nm in diameter. Recent studies have suggested that nanocrystals (<200 nm) elicit more injury to renal cells compared to microcrystals. The purpose of this study was to determine whether (i) urinary nanocrystals can be detected and quantified by nanoparticle tracking analysis (NTA, a high-resolution imaging technology), (ii) early-void urine samples from healthy subjects contain calcium nanocrystals, and (iii) a dietary oxalate load increases urinary nanocrystal formation.MethodsHealthy subjects consumed a controlled low-oxalate diet for 3 days before a dietary oxalate load. Urinary crystals were isolated by centrifugation and assessed using NTA before and 5 hours after the oxalate load. The morphology and chemical composition of crystals was assessed using electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and ion chromatography-mass spectrometry (IC–MS).ResultsUrinary calcium oxalate nanocrystals were detected in pre-load samples and increased substantially following the oxalate load.ConclusionThese findings indicate that NTA can quantify urinary nanocrystals and that meals rich in oxalate can promote nanocrystalluria. NTA should provide valuable insight about the role of nanocrystals in kidney stone formation.

SUN-331 COMBINED LIVER KIDNEY TRANSPLANTATION FOR PRIMARY HYPEROXALURIA: SINGLE CENTRE EXPERIENCE IN SOUTH INDIA

Type 1 primary hyperoxaluria is a rare inherited autosomal recessive disorder, characterized by deficiency of the hepatic enzyme alanine glyoxylate aminotransferase, leading to increased oxalate production, nephrocalcinosis, urolithiasis, and systemic oxalosis. Early diagnosis and management is pivotal as medical management and definitive treatment in the form of combined or sequential liver-kidney transplantation, isolated liver or kidney transplantation have been studied to transform disease outcomes. Here, we review the experience from our institution of combined liver-kidney transplantation among patients with primary hyperoxaluria from February, 2014 to October, 2019. Among three children with primary hyperoxaluria, two underwent deceased donor liver-kidney transplantation, and the third live related donor sequential liver-kidney transplantation. Case 1 was that of a 17 year old boy, who had been on intensive daily dialysis for two years prior to deceased donor sequential liver-kidney transplantation, with a history of bladder calculus in childhood. He had a relatively uneventful post -transplant period and is doing well on follow up five years following transplantation. Case 2 was a 4 year old boy, diagnosed to have oxalosis two years prior to transplant, on dialysis five days a week through tunnelled catheter, prior to deceased donor liver-kidney transplantation, with a history of tonic-clonic seizures. Post-operatively, he had a stormy course with cytomegalovirus infection of the hepatic allograft, and hepatic artery thrombosis, and expired a month following transplantation. Case 3 was that of a 13 year old girl, diagnosed at 10 years of age with primary hyperoxaluria, who underwent live related donor sequential liver-kidney transplantation. She developed obstructive jaundice following liver transplantation, owing to biliary stricture, and underwent ERCP and biliary stenting. She also had an upper gastro -intestinal bleed, and profound anaemia, and later developed sepsis and cholangitis, which were conservatively managed. Subsequently, she underwent renal transplantation and later developed gram negative septicemia, and recurrent proximal bile duct stricture, which was subjected to biliary stenting. Presently, she has stable graft function, and is clinically stable. The experience from our institution re-emphasises the significance of early diagnosis, and pre-transplant intensive dialysis in reducing oxalate load if planning for sequential liver-kidney transplantation to improve outcomes in primary hyperoxaluria. Isolated liver or kidney transplantation have not been adopted in our centre. In all patients, Scheinman protocol was followed in the immediate post-transplant period. Renal biopsies in the recipient showed only mild oxalate deposits which did not affect graft survival.

Stiripentol for the treatment of primary hyperoxaluria and calcium oxalate nephropathy

Oxalate is one of several potentially toxic metabolites that must be eliminated by the kidneys to avoid harmful effects. In healthy individuals, variable amounts of food-derived oxalate are delivered to the kidneys and entirely excreted by glomerular filtration and tubular secretion. Excessive delivery of oxalate to the kidneys causes increased urinary oxalate excretion, and when the oxalate load becomes excessive, urinary oxalate supersaturation may lead to calcium oxalate crystal formation. This crystal formation favors the development of calcium oxalate stones and the deposition of calcium oxalate crystals in the kidneys.

MP24-19 ENTERAL NUTRITION FORMULAS WITH HIGHER OXALATE CONTENT MAY CONTRIBUTE TO HIGHER OXALATE ABSORPTION AND URINARY EXCRETION IN PATIENTS REQUIRING NUTRITION SUPPORT

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology II1 Apr 2018MP24-19 ENTERAL NUTRITION FORMULAS WITH HIGHER OXALATE CONTENT MAY CONTRIBUTE TO HIGHER OXALATE ABSORPTION AND URINARY EXCRETION IN PATIENTS REQUIRING NUTRITION SUPPORT Kristina L. Penniston, Eve A. Palmer, Riley C. Medenwald, Sarah N. Johnson, Leema M. John, David J. Beshensky, and Ibrahim A. Saeed Kristina L. PennistonKristina L. Penniston More articles by this author , Eve A. PalmerEve A. Palmer More articles by this author , Riley C. MedenwaldRiley C. Medenwald More articles by this author , Sarah N. JohnsonSarah N. Johnson More articles by this author , Leema M. JohnLeema M. John More articles by this author , David J. BeshenskyDavid J. Beshensky More articles by this author , and Ibrahim A. SaeedIbrahim A. Saeed More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.772AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients requiring oral and/or enteral nutrition support for nutritional needs can form calcium oxalate (CaOx) kidney stones. Dietary oxalate, if excessive, can contribute to CaOx stones when unopposed by appropriate calcium. The oxalate concentration of oral/enteral nutrition formulas is not known. We assessed various formulas for oxalate. METHODS Adult and pediatric oral/enteral nutrition formulas commonly used in hospitals as well as in home feeding regimens were selected. Formulas designed for oral and enteral consumption (or either) were included (table); completely elemental (hydrolyzed) or modular formula products were not. Multiple samples (N, table) of each formula were acidified, heated, and centrifuged. Supernatants were filtered and analyzed for oxalate by ion chromatography. Oxalate concentration (mg/L±SD), relative standard deviation (SD) between samples (coefficient of variation; CV), and calcium:oxalate ratios (mg:mg/L of formula) were calculated. RESULTS Of 35 formulas analyzed, 9 were excluded due to inconsistent results and high CVs. Results for the 26 remaining formulas are shown (table). Oxalate concentration ranged from 4-140 mg oxalate/L of formula. Due to highly variable calcium content, calcium:oxalate ratios varied widely between formulas (from 0-286) with lower ratios suggesting higher potential for oxalate absorption. There was no difference between mean oxalate concentration of enteral vs. oral formulas (45 vs. 46 mg/L; P=0.92). Formulas designated for enteral use tended to have lower relative SDs (mean CV 16% vs. 21% for oral formulas), likely due to the generally more complex matrix of oral formulas, which contributed to more analytical variability. Depending on the formula, a patient requiring 1.5 L daily could obtain anywhere from 12-150 mg oxalate. CONCLUSIONS Patients requiring oral and/or enteral nutrition support are at risk for a high exogenous oxalate load depending on the formula ingested and on the bioavailability of oxalate. Patients with a history of or at high risk for urolithiasis would benefit from strategies to reduce the bioavailability of oxalate and urinary oxalate excretion, which may include supplemental calcium with feedings or use of an appropriate lower oxalate formula. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e297-e298 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kristina L. Penniston More articles by this author Eve A. Palmer More articles by this author Riley C. Medenwald More articles by this author Sarah N. Johnson More articles by this author Leema M. John More articles by this author David J. Beshensky More articles by this author Ibrahim A. Saeed More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Compliance in patients with dietary hyperoxaluria: A cohort study and systematic review

ObjectiveHyperoxaluria leads to calcium oxalate crystal formation and subsequent urolithiasis. This study aims to analyse the effect of treatment compliance in hyperoxaluria, firstly by analysis of patients with non-primary hyperoxaluria and secondly via systematic review in patients with any hyperoxaluria. MethodsIn a retrospective cohort study, adults with non-primary hyperoxaluria managed with dietary counselling in 2013 were enrolled. Twenty-four-hour (24 h) urine collections initially and at 6 months were obtained. Compliance was assessed by self-reported dietary compliance and 24 h urinary volume >2 L. Patients were followed for 24 months. Primary outcomes were urinary oxalate and calcium 24 h load at 6 months, and urolithiasis-related procedural rates at 24 months. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compatible systematic review of compliance among hyperoxaluric patients was performed. ResultsIn the cohort study, of 19 eligible patients (4 female) with median age 52 years, 10 (53%) were considered compliant. Compared with the non-compliant group, these patients had significantly increased subsequent 24 h urinary volume (2250 mL vs. 1600 mL; p = 0.008) and lower procedural rates (10% vs. 56%; p = 0.033). Subsequent 24 h urinary oxalate load was non-significantly lower in compliant patients. Systematic review regarding compliance in hyperoxaluric patients revealed five studies. Only one utilised dietary counselling or analysed compliant vs. non-compliant patients, finding no difference. None examined the effect of compliance on procedural rates. ConclusionHyperoxaluria is an important cause of recurrent urolithiasis. Increasing fluid intake and reducing dietary oxalate reduce the risk of operative intervention and remain fundamental to the treatment of hyperoxaluria.

Dietary oxalate induces monocyte mitochondrial dysfunction and crystalluria in healthy subjects: A role of spinach in kidney stone disease?

Dietary oxalate contributes significantly to urinary oxalate excretion and is linked to calcium oxalate kidney stone formation. Oxalate is a common component found in kidney stones and in plants such as spinach. We have previously shown that patients with calcium oxalate kidney stone disease have decreased mitochondrial function and increased IL‐6 levels compared to healthy subjects. The purpose of this study was to investigate whether a dietary oxalate load has any effect on monocyte mitochondrial function and urinary oxalate levels in healthy subjects. Nine healthy subjects between the ages of 21 and 31 with an average BMI of 24.6 ±1.2 were included in the study. Participants consumed a low oxalate diet for 3 days prior to drinking a high dietary oxalate load (spinach smoothie). Blood and urine was collected from participants prior to consuming a high oxalate spinach load (pre‐smoothie) and 5 hours following smoothie consumption (post‐smoothie). Monocyte mitochondrial function was measured using Seahorse XF96 technology. Urinary oxalate levels (both crystalline and soluble) were determined using ion chromatography‐mass spectrometry. The high dietary oxalate load caused a significant decrease in monocyte mitochondrial function in healthy subjects. These responses were similar to levels previously found in patients with calcium oxalate kidney stone disease. In addition, both crystalline and soluble urinary oxalate levels were significantly increased in post‐smoothie samples compared to pre‐smoothie samples. These findings suggest that a high dietary oxalate could affect monocyte mitochondrial function in patients. Future studies will investigate potential mechanisms responsible for these findings.Support or Funding InformationThis work was supported by NIH K01DK106284 and the UAB Department of Urology.

Primary hyperoxaluria in infants.

The infantile form of primary hyperoxaluria type-1 (PH-1) is characterized by a rapid progression to the end-stage renal disease (ESRD) due to both increased oxalate load and reduced glomerular filtration rate. In the literature, data on this form are limited. The purpose of this study is to analyze retrospectively the clinical, biological, and radiological features of children who were diagnosed with PH-1 during the 1(st) year of life. We reviewed the records of all children with PH-1 diagnosed and followed-up at our department between January 1995 and December 2013. Among them, only infants younger than 12 months of age were retrospectively enrolled in the study. Fourteen infants with the median age of two months were enrolled in the study. At diagnosis, 11 patients had ESRD. All patients had nephrocalcinosis and two of them had calculi. The diagnosis was established in nine patients on the basis of the positive family history of PH-1, bilateral nephrocalcinosis, and quantitative crystalluria. In four patients, the diagnosis was made with molecular analysis of DNA. Kidney biopsy contributed to the diagnosis in one patient. During follow-up, two patients were pyridoxine sensitive and preserved renal function. Seven among 11 patients who had ESRD died, four patients are currently undergoing peritoneal dialysis. Children with infantile PH and ESRD are at high risk of early death. Peritoneal dialysis is not a treatment of choice. Combined liver-kidney transplantation is mandatory.

Effect of Blending and the Simultaneous Ingestion of a Probiotic Containing Oxalate-Degrading Bacteria on Oxalate Absorption

Both a high dietary oxalate intake and increased gastrointestinal absorption can lead to elevated urinary oxalate, a risk factor for kidney stone formation. Numerous studies have assessed whether daily ingestion of a probiotic containing oxalate-degrading bacteria can reduce urinary oxalate/oxalate absorption, but it appears only one previous study assessed whether the simultaneous ingestion of oxalate-degrading probiotic bacteria consumed with an oxalate load can exert this effect. This was assessed in the present study in a population of 11 healthy non-stone formers (6 males, 5 females), aged 21 – 37 y, using the probiotic VSL#3&lt;sup&gt;®&lt;/sup&gt;. A spinach-sweet potato mixture provided an oxalate dose of 534 mg and urine samples were collected for a 22 h period post-oxalate ingestion. An additional objective was to assess the effect of blending oxalate-containing foods on oxalate absorption. The overall results suggested that the spinach and sweet potato provided oxalate of low bioavailability. Changing the texture of these foods by blending did not have an effect on oxalate absorption nor was VSL#3&lt;sup&gt;®&lt;/sup&gt; effective in reducing urinary oxalate levels. VSL#3&lt;sup&gt;®&lt;/sup&gt; may have been more effective if the oxalate dose had been provided in a more bioavailable form leading to a higher initial oxalate absorption/urinary oxalate excretion.

Potential role of fluctuations in the composition of renal tubular fluid through the nephron in the initiation of Randall's plugs and calcium oxalate crystalluria in a computer model of renal function.

Potential role of fluctuations in the composition of renal tubular fluid through the nephron in the initiation of Randall's plugs and calcium oxalate crystalluria in a computer model of renal function.