oxalates and Renal-Insufficiency--Chronic

Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions.

Topics: Homeostasis; Humans; Hyperoxaluria; Kidney; Oxalates; Renal Dialysis; Renal Insufficiency; Renal Insufficiency, Chronic

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.. 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.. In the near future, there will likely be therapies targeting both endogenous and dietary oxalate, especially in subsets of kidney stone formers.

Topics: Adult; Animals; Diet; Humans; Hyperoxaluria; Kidney Calculi; Mice; Oxalates; Rats; Renal Insufficiency, Chronic

Both chronic kidney disease (CKD) and kidney stones are major public health problems, which are closely interrelated. Recurrent kidney stones predispose to CKD although CKD seems to decrease risk of further kidney stone formation. Herein, we review new information of this interrelationship.. Several epidemiological studies in the past have shown an association between history of kidney stones and risk for CKD and CKD progression. Recent literature supports this concept and it is reviewed in this article. The issue of whether CKD protects against new kidney stone formation remains unsettled and there is no recent literature addressing it. In relation to stone risk factors in CKD, there are several interesting new articles that discuss mechanisms of hypocitraturia in early CKD before overt metabolic acidosis. Since hypocitraturia is an important risk factor for kidney stone formation we addressed these new data in detail. There are also new data supporting urinary oxalate excretion as a predictor of CKD progression.. It seems clear that recurrent kidney stones should be avoided not only because of their immediate clinical manifestations but also because of their long-term predisposition to CKD progression. Mechanisms leading to hypocitraturia in early CKD still remain controversial.

Topics: Citric Acid; Humans; Kidney Calculi; Oxalates; Renal Insufficiency, Chronic

Accurate risk stratification in patients with chronic kidney disease (CKD) is highly desirable to help guide earlier, targeted treatment in high-risk individuals. In this review, we report recent developments in our understanding of risk factors and risk prediction in patients with CKD.. A large meta-analysis has shown that conventional cardiovascular risk factors continue to play an important role in disease progression and adverse outcomes in patients with advanced CKD where the estimated glomerular filtration rate (eGFR) is < 30 ml/min/1.73 m). Several studies have shed light on novel biomarkers in CKD, including peptides (LG1 M), genes (MUC1) and metabolic factors (urinary oxalate excretion). Cortical oxygenation measured by BOLD-MRI also provides a novel radiological measure predictive of future eGFR decline. A new risk prediction score for patients with CKD G4-5 has been developed, offering an aid to decision-making in these patients.. Ongoing work across various disciplines continues to unravel the determinants of CKD progression. A few notable risk prediction tools in CKD have now surfaced but whether they can be utilised to offer improved care remains a key unanswered question.

Topics: Biomarkers; Glomerular Filtration Rate; Humans; Mucin-1; Oxalates; Renal Insufficiency, Chronic; Risk Factors

Hyperoxaluria can cause kidney disease through multiple mechanisms, including tubular obstruction from calcium oxalate crystals, sterile inflammation, and tubular epithelial cell injury. Hyperoxaluria is also observed in individuals with diabetes mellitus and obesity, which are in turn risk factors for chronic kidney disease (CKD). Whether hyperoxaluria is a potential mediator of increased risk of CKD in diabetes mellitus and obesity is unknown.. Individuals with diabetes have increased levels of plasma glyoxal (a protein glycation product) and glyoxylate, both of which are precursors for oxalate. Increased gut absorption of oxalate in obesity may be because of obesity-associated inflammation. A recent study in individuals with CKD found that higher 24 h urinary oxalate excretion was independently associated with increased risk of kidney disease progression, especially in individuals with diabetes and obesity.. Both diabetes mellitus and obesity are associated with higher urinary oxalate excretion through distinct mechanisms. Hyperoxaluria could be a mechanism by which kidney disease develops in individuals with diabetes mellitus or obesity and could also contribute to progressive loss of renal function. Future research on pharmacologic or dietary measures to limit oxalate absorption or generation are required to test whether lowering urinary oxalate excretion is beneficial in preventing kidney disease development and progression in diabetes mellitus and obesity.

Topics: Diabetic Nephropathies; Humans; Hyperoxaluria; Inflammation; Obesity; Oxalates; Renal Insufficiency, Chronic

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

Topics: Cardiovascular Diseases; Carnitine; Choline; Diet; Gastrointestinal Microbiome; Humans; Methylamines; Micronutrients; Oxalates; Phosphates; Phosphatidylcholines; Renal Insufficiency, Chronic; Tryptophan; Tyrosine

Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis, and progressive renal failure. It has long been known that as the glomerular filtration rate becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary cause.. The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the NOD-like receptor family, pyrin domain containing 3 inflammasome (also known as NALP3, NLRP3, or cryopyrin), resulting in release of IL-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure.. The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.

Topics: Animals; Disease Progression; Fibrosis; Humans; Inflammasomes; Inflammation; Interleukin-1beta; Kidney; Macrophages; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Oxalates; Renal Insufficiency, Chronic

In patients with primary hyperoxaluria (PH), endogenous oxalate overproduction increases urinary oxalate excretion, leading to compromised kidney function and often kidney failure. Highly elevated plasma oxalate (Pox) is associated with systemic oxalate deposition in patients with PH and severe chronic kidney disease (CKD). The relationship between Pox and estimated glomerular filtration rate (eGFR) in patients with preserved kidney function, however, is not well established. Our analysis aimed to investigate a potential correlation between these parameters in PH patients from three randomized, placebo-controlled trials (studies OC3-DB-01, OC3-DB-02, and OC5-DB-01).. Baseline data from patients with a PH diagnosis (type 1, 2, or 3) and eGFR > 40 mL/min/1.73 m. A total of 106 patients were analyzed. A statistically significant inverse Spearman's correlation between eGFR and Pox was observed across all analyses; correlation coefficients were - 0.44 in study OC3-DB-01, - 0.55 in study OC3-DB-02, - 0.51 in study OC5-DB-01, and - 0.49 in the pooled studies (p < 0.0064).. Baseline evaluations showed a moderate and statistically significant inverse correlation between eGFR and Pox in patients with PH already at early stages of CKD (stages 1-3b), demonstrating that a correlation is present before substantial loss in kidney function occurs.

Topics: Glomerular Filtration Rate; Humans; Hyperoxaluria, Primary; Hyperplasia; Kidney; Oxalates; Renal Insufficiency, Chronic

Kidney stones (KSs) are very common, excruciating, and associated with tremendous healthcare cost, chronic kidney disease (CKD), and kidney failure (KF). Most KSs are composed of calcium oxalate and small increases in urinary oxalate concentration significantly enhance the stone risk. Oxalate also potentially contributes to CKD progression, kidney disease-associated cardiovascular diseases, and poor renal allograft survival. This emphasizes the urgent need for plasma and urinary oxalate lowering therapies, which can be achieved by enhancing enteric oxalate secretion. We previously identified

Topics: Animals; Caco-2 Cells; Epithelial Cells; Humans; Hyperoxaluria; Kidney Calculi; Kidney Transplantation; Mice; Oxalates; Oxalobacter formigenes; Peptides; Renal Insufficiency; Renal Insufficiency, Chronic

Calcium oxalate (CaOx) stones are among the most common types of kidney stones and are associated with renal tubular damage, interstitial fibrosis, and chronic kidney disease. The mechanism of CaOx crystal-induced renal fibrosis remains unknown. Ferroptosis, a type of regulated cell death, is characterised by iron-dependent lipid peroxidation, and the tumour suppressor p53 is a key regulator of ferroptosis. In the present study, our results demonstrated that ferroptosis was significantly activated in patients with nephrolithiasis and hyperoxaluric mice as well as verified the protective effects of ferroptosis inhibition on CaOx crystal-induced renal fibrosis. Moreover, the single-cell sequencing database, RNA-sequencing, and western blot analysis revealed that the expression of p53 was increased in patients with chronic kidney disease and the oxalate-stimulated human renal tubular epithelial cell line, HK-2. Additionally, the acetylation of p53 was enhanced by oxalate stimulation in HK-2 cells. Mechanistically, we found that the induction of p53 deacetylation, owing to either the SRT1720-induced activation of deacetylase sirtuin 1 or the triple mutation of p53, inhibited ferroptosis and alleviated renal fibrosis caused by CaOx crystals. We conclude that ferroptosis is one of the critical mechanisms contributing to CaOx crystal-induced renal fibrosis, and the pharmacological induction of ferroptosis via sirtuin 1-mediated p53 deacetylation may be a potential target for preventing renal fibrosis in patients with nephrolithiasis.

Topics: Animals; Calcinosis; Calcium Oxalate; Ferroptosis; Fibrosis; Humans; Kidney; Kidney Calculi; Mice; Oxalates; Renal Insufficiency, Chronic; Sirtuin 1; Tumor Suppressor Protein p53

Urolithiasis is a known risk factor for chronic kidney disease (CKD). However, how CKD might affect the risk of incidence of urolithiasis is not widely studied.. Urinary excretion of oxalate as well as other key factors related to urolithiasis was analyzed in a single center study of 572 patients with biopsy-proven kidney disease.. Excretion of oxalate and other key factors related to urolithiasis was differentially associated with eGFR, urinary protein, and pathological changes in CKD patients. The influence of these intrinsic traits of the underlining kidney disease should be considered when evaluating urolithiasis risk in patients with CKD.

Topics: Female; Humans; Incidence; Male; Middle Aged; Oxalates; Renal Insufficiency, Chronic; Urolithiasis

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) (

Topics: Animals; Blood Pressure; Diet; Hypertension; Kidney; Oxalates; Rats; Rats, Inbred Dahl; Renal Insufficiency, Chronic; Sodium Chloride; Sodium Chloride, Dietary

Intrarenal extracellular matrix production or kidney fibrosis is a prevalent feature of all forms of chronic kidney disease (CKD). The transforming growth factor-beta (TGFβ) is believed to be a major driver of extracellular matrix production. Nevertheless, anti-TGFβ therapies have consistently failed to reduce extracellular matrix production in CKD patients indicating the need for novel therapeutic strategies. We have previously shown that necroinflammation contributes to acute kidney injury. Here, we show that chronic/persistent necroinflammation drives intrarenal extracellular matrix production during CKD. We found that renal expression of receptor-interacting protein kinase-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) increases with the production of intrarenal extracellular matrix and declined kidney function in both humans and mice. Furthermore, we found that TGFβ exposure induces the translocation of RIPK3 and MLKL to mitochondria resulting in mitochondrial dysfunction and ROS production. Mitochondrial ROS activates the serine-threonine kinase calcium/calmodulin-dependent protein kinases-II (CaMKII) that increases phosphorylation of Smad2/3 and subsequent production of alpha-smooth muscle actin (αSMA), collagen (Col) 1α1, etc. in response to TGFβ during the intrarenal extracellular matrix production. Consistent with this, deficiency or knockdown of RIPK3 or MLKL as well as pharmacological inhibition of RIPK1, RIPK3, and CaMKII prevents the intrarenal extracellular matrix production in oxalate-induced CKD and unilateral ureteral obstruction (UUO). Together, RIPK1, RIPK3, MLKL, CaMKII, and Smad2/3 are molecular targets to inhibit intrarenal extracellular matrix production and preserve kidney function during CKD.

Topics: Actins; Animals; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Extracellular Matrix; Humans; Mice; Mitochondria; Oxalates; Protein Kinases; Reactive Oxygen Species; Receptor-Interacting Protein Serine-Threonine Kinases; Renal Insufficiency, Chronic; Transforming Growth Factors

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. Our objective was to compare concentrations of ingredients important for kidney stones and chronic kidney disease in popular brands of milk alternatives.. Sodium, calcium, and potassium contents were obtained from nutrition labels. The oxalate content was measured by ion chromatography coupled with mass spectrometry.. The calcium content is highest in macadamia followed by soy, almond, rice, and dairy milk; it is lowest in cashew, hazelnut, and coconut milk. Almond milk has the highest oxalate concentration, followed by cashew, hazelnut, and soy. Coconut and flax milk have undetectable oxalate levels; coconut milk also has comparatively low sodium, calcium, and potassium, while flax milk has the most sodium. Overall, oat milk has the most similar parameters to dairy milk (moderate calcium, potassium and sodium with low oxalate). Rice, macadamia, and soy milk also have similar parameters to dairy milk.. As consumption of plant-based dairy substitutes increases, it is important for healthcare providers and patients with renal conditions to be aware of their nutritional composition. Oat, macadamia, rice, and soy milk compare favorably in terms of kidney stone risk factors with dairy milk, whereas almond and cashew milk have more potential stone risk factors. Coconut milk may be a favorable dairy substitute for patients with chronic kidney disease based on low potassium, sodium, and oxalate. Further study is warranted to determine the effect of plant-based milk alternatives on urine chemistry.

Topics: Animals; Calcium; Calcium, Dietary; Diet, Sodium-Restricted; Female; Humans; Kidney Calculi; Male; Oxalates; Potassium; Renal Insufficiency, Chronic; Risk Factors; Sodium

Blood biomarkers of dietary intake are more objective than self-reported dietary intake. Metabolites associated with dietary acid load were previously identified in 2 chronic kidney disease (CKD) populations. We aimed to extend these findings to a general population, replicating their association with dietary acid load, and investigating whether the individual biomarkers were prospectively associated with incident CKD.. Among 15,792 participants in the Atherosclerosis Risk in Communities cohort followed up from 1987 to 1989 (baseline) to 2019, we evaluated 3,844 black and white men and women with dietary and metabolomic data in cross-sectional and prospective analyses. We hypothesized that a higher dietary acid load (using equations for potential renal acid load and net endogenous acid production) was associated with lower serum levels of 12 previously identified metabolites: indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine, threonate, oxalate, chiro-inositol, methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate. In addition, we hypothesized that lower serum levels of these 12 metabolites were associated with higher risk of incident CKD.. Eleven out of 12 metabolites were significantly inversely associated with dietary acid load, after adjusting for demographics, socioeconomic status, health behaviors, health status, and estimated glomerular filtration rate: indolepropionylglycine, indolepropionate, N-methylproline, threonate, oxalate, chiro-inositol, catechol sulfate, hippurate, methyl glucopyranoside (α + β), stachydrine, and tartronate. N-methylproline was inversely associated with incident CKD (hazard ratio: 0.95, 95% confidence interval: 0.91, 0.99, P = .01). The metabolomic biomarkers of dietary acid load significantly improved prediction of elevated dietary acid load estimated using dietary data, beyond covariates (difference in C statistics: 0.021-0.077, P ≤ 1.08 × 10. Inverse associations between candidate biomarkers of dietary acid load were replicated in a general population. N-methylproline, representative of citrus fruit consumption, is a promising marker of dietary acid load and could represent an important pathway between dietary acid load and CKD.

Topics: Biomarkers; Catechols; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Hippurates; Humans; Incidence; Inositol; Male; Metabolomics; Oxalates; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Sulfates; Tartronates

Vitamin C deficiency is common in chronic kidney disease (CKD) due to losses through dialysis and dietary intake below requirement. We investigated prevalence of vitamin C deficiency and impact of vitamin C treatment in deficient/insufficient patients.. A prospective cohort study in patients aged 1-18 years with CKD stages 4 and 5D collected demographic data including underlying disease, treatment, and anthropometric assessment. Vitamin C intake was assessed using 24-h dietary recall. Hemoglobin, iron status, serum vitamin C, and serum oxalate were measured at baseline and after treatment. Vitamin C (250 mg/day) was given orally for 3 months to deficient/insufficient patients.. Nineteen patients (mean age 12.00 ± 4.1 years) showed prevalence of 10.6% vitamin C insufficiency and 78.9% deficiency. There were no associations between vitamin C level and daily vitamin C intake (p = 0.64) or nutritional status (p = 0.87). Median serum vitamin C was 1.51 (0.30-1.90) mg/L. In 16 patients receiving treatment, median serum vitamin C increased from 1.30 (0.23-1.78) to 3.22 (1.77-5.96) mg/L (p = 0.008) without increasing serum oxalate (79.92 (56.6-106.84) vs. 80.47 (56.88-102.95) μmol/L, p = 0.82). However, 62.5% failed to achieve normal vitamin C levels. Ordinal regression analysis revealed patients with non-oligoanuric CKD were less likely to achieve normal vitamin C levels (β = - 3.41, p = 0.03).. We describe high prevalence of vitamin C insufficiency/deficiency among pediatric CKD patients. Vitamin C levels could not be solely predicted by nutritional status or daily intake. The treatment regimen raised serum vitamin C without increasing serum oxalate; however, it was largely insufficient to normalize levels, particularly in non-oligoanuric CKD. Graphical abstract .

Topics: Adolescent; Ascorbic Acid; Ascorbic Acid Deficiency; Child; Humans; Oxalates; Prevalence; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency; Vitamins

Malnutrition and anorexia are common in children with chronic kidney disease (CKD) and gastrostomy tubes (GT) as well as nasogastric tubes (NGT) have been recommended to maximize nutritional support. The optimal requirement of vitamin C in children with CKD remains to be defined but oxalate is a breakdown product of vitamin C. Elevated vitamin C intake and bone oxalate were identified in two formula-fed dialyzed children with negative genetic testing for primary hyperoxaluria.. We evaluated the impact of nutritional support on serum ascorbic acid and plasma oxalate levels in 13 dialyzed infants and young children.. All patients were fed by GT or NGT since the first months of life; overall patients were receiving between 145 and 847% of the age-specific DRI for vitamin C. Mean serum ascorbic acid and plasma oxalate levels were elevated (244.7 ± 139.7 μM/L and 44.3 ± 23.1 μM/L, respectively), and values did not differ according to the degree of residual kidney function. Ascorbic acid levels did not correlate with oxalate levels (r = 0.44, p = 0.13).. Excessive vitamin C intake may contribute to oxalate accumulation in dialyzed children.

Topics: Ascorbic Acid; Child; Child, Preschool; Humans; Hyperoxaluria; Infant; Kidney Failure, Chronic; Oxalates; Renal Dialysis; Renal Insufficiency, Chronic; Vitamins

Topics: Adult; Female; Homozygote; Humans; Hyperoxaluria, Primary; Kidney Failure, Chronic; Middle Aged; Oxalates; Pyridoxine; Recovery of Function; Renal Dialysis; Renal Insufficiency, Chronic; Transaminases; Vitamin B Complex; Young Adult

A 73-year-old Caucasian female with a history of obesity status post Roux-en-Y gastric bypass (RYGB) surgery presented with generalized weakness and was found to have acute kidney injury (AKI) with a creatinine peak of 9.1 mg/dL above her baseline of 1.2 mg/dL, and anemia with hemoglobin 5.7 g/dl. Kidney biopsy revealed oxalate nephropathy likely related to gastric bypass surgery four years prior. RYGB is a strong risk factor for hyperoxaluria, nephrolithiasis, and oxalate nephropathy which often progresses to end-stage renal disease (ESRD). Meaningful treatment strategies for this disease entity are lacking. We present a case in which dietary and pharmacological management without the use of renal replacement therapy resulted in stabilization of chronic kidney disease (CKD) stage 5 for seven years at the time of this writing.

Topics: Aged; Female; Gastric Bypass; Humans; Hyperoxaluria; Obesity; Oxalates; Postoperative Complications; Renal Insufficiency, Chronic

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.. 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).. 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.. 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.

Topics: Animals; Atherosclerosis; Cell Line; Disease Models, Animal; Endothelial Cells; Humans; Male; Mice; Oxalates; Oxidative Stress; Renal Insufficiency, Chronic; Uremia; Vascular Calcification

Topics: Calcium Oxalate; Humans; Kidney Calculi; Nephrolithiasis; Oxalates; Renal Insufficiency, Chronic; Retrospective Studies

A state of oxalate homeostasis is maintained in patients with healthy kidney function. However, as GFR declines, plasma oxalate (P. Feeding a diet high in soluble oxalate or weekly injections of aristolochic acid induced CKD in age- and sex-matched wild-type and. Fecal oxalate excretion was enhanced in wild-type mice with CKD. This increase was abrogated in. Slc26a6-mediated enteric oxalate secretion is critical in decreasing the body burden of oxalate in murine CKD models. Future studies are needed to address whether similar mechanisms contribute to intestinal oxalate elimination in humans to enhance extrarenal oxalate clearance.

Topics: Animals; Antiporters; Disease Models, Animal; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Oxalates; Renal Insufficiency, Chronic; Sulfate Transporters

Oxalate is a metabolite consumed in nuts, beans and leaves, and excreted in urine. Oxalosis can cause nephropathy. We describe a rare case of a high-oxalate diet intended for irritable bowel syndrome (IBS) treatment causing oxalate nephropathy. A 59-year-old woman with a history of controlled hypertension presented with creatinine 1.8 mg/dL, increased from baseline 1.3 mg/dL. She denied recent illness, urinary stones, medication adjustments, herbal supplements and non-steroidal anti-inflammatory drugs use. Diet included six tablespoons of chia seeds and five handfuls of almonds daily to manage IBS symptoms. Her electrolytes, urinalysis and renal ultrasound were unremarkable. Her 24-hour urine output revealed increased oxalate and low citrate. Renal biopsy showed glomerulosclerosis, fibrosis and calcium oxalate deposition. She switched to a low-oxalate diet, with improvement in laboratory markers. An earlier dietary history could have raised concern for oxalosis prior to renal biopsy. Providers should be trained to identify at-risk patients and provide appropriate dietary counselling.

Topics: Calcium Oxalate; Creatinine; Diet; Female; Glomerulonephritis; Humans; Hyperoxaluria; Kidney; Middle Aged; Nuts; Oxalates; Prunus dulcis; Renal Insufficiency, Chronic; Seeds

Oxalate is a potentially toxic terminal metabolite that is eliminated primarily by the kidneys. Oxalate nephropathy is a well-known complication of rare genetic disorders and enteric hyperoxaluria, but oxalate has not been investigated as a potential contributor to more common forms of chronic kidney disease (CKD).. To assess whether urinary oxalate excretion is a risk factor for more rapid progression of CKD toward kidney failure.. This prospective cohort study assessed 3123 participants with stages 2 to 4 CKD who enrolled in the Chronic Renal Insufficiency Cohort study from June 1, 2003, to September 30, 2008. Data analysis was performed from October 24, 2017, to June 17, 2018.. Twenty-four-hour urinary oxalate excretion.. A 50% decline in estimated glomerular filtration rate (eGFR) and end-stage renal disease (ESRD).. This study included 3123 participants (mean [SD] age, 59.1 [10.6] years; 1414 [45.3%] female; 1423 [45.6%] white). Mean (SD) eGFR at the time of 24-hour urine collection was 42.9 (16.8) mL/min/1.73 m2. Median urinary excretion of oxalate was 18.6 mg/24 hours (interquartile range [IQR], 12.9-25.7 mg/24 hours) and was correlated inversely with eGFR (r = -0.13, P < .001) and positively with 24-hour proteinuria (r = 0.22, P < .001). During 22 318 person-years of follow-up, 752 individuals reached ESRD, and 940 individuals reached the composite end point of ESRD or 50% decline in eGFR (CKD progression). Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD: compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression (hazard ratio [HR], 1.33; 95% CI, 1.04-1.70) and a 45% higher risk of ESRD (HR, 1.45; 95% CI, 1.09-1.93). The association between oxalate excretion and CKD progression and ESRD was nonlinear and exhibited a threshold effect at quintiles 3 to 5 vs quintiles 1 and 2. Higher vs lower oxalate excretion (at the 40th percentile) was associated with a 32% higher risk of CKD progression (HR, 1.32; 95% CI, 1.13-1.53) and 37% higher risk of ESRD (HR, 1.37; 95% CI, 1.15-1.63). Results were similar when treating death as a competing event.. Higher 24-hour urinary oxalate excretion may be a risk factor for CKD progression and ESRD in individuals with CKD stages 2 to 4.

Topics: Adult; Aged; Biomarkers; Disease Progression; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Male; Middle Aged; Oxalates; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; Survival Rate; United States; Young Adult

Topics: Disease Progression; Humans; Oxalates; Renal Insufficiency, Chronic; Risk Factors

Topics: Creatinine; Glomerular Filtration Rate; Humans; Oxalates; Renal Insufficiency, Chronic

Topics: Calcium Oxalate; Humans; Oxalates; Renal Insufficiency, Chronic

Topics: Calcium Oxalate; Humans; Oxalates; Renal Insufficiency, Chronic

Topics: Gastrointestinal Microbiome; Humans; Oxalates; Oxalic Acid; Oxalobacter formigenes; Renal Insufficiency, Chronic

Topics: Animals; Calcium Oxalate; Crystallization; Diet; Disease Models, Animal; Fibrosis; Glomerular Filtration Rate; Humans; Immunoglobulin G; Kidney; Male; Mice; Mice, Inbred C57BL; Nephrocalcinosis; Oxalates; Renal Insufficiency, Chronic; Transforming Growth Factor beta

Topics: Anacardium; Calcium Carbonate; Chelating Agents; Female; Humans; Hyperoxaluria; Middle Aged; Nuts; Oxalates; Renal Insufficiency, Chronic

Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits.. The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis.. These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.

Topics: Acute Kidney Injury; Averrhoa; Female; Fruit; Humans; Male; Middle Aged; Oxalates; Renal Insufficiency, Chronic

Topics: Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Nephrectomy; Oxalates; Oxalic Acid; Renal Insufficiency, Chronic