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Nutrients Sep 2020Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based... (Review)
Review
Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to promote antioxidant defense and reduce inflammation. While recommendations encourage the intake of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase plant-food consumption, there have been some concerns raised about whether they are beneficial because of the various 'anti-nutrient' compounds they contain. Some of these anti-nutrients that have been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins. As a result, there may be select individuals with specific health conditions who elect to decrease their plant food intake despite potential benefits. The purpose of this narrative review is to examine the science of these 'anti-nutrients' and weigh the evidence of whether these compounds pose an actual health threat.
Topics: Antioxidants; Antithyroid Agents; Cooking; Diet, Vegetarian; Food Handling; Fruit; Humans; Lectins; Nutrients; Oxalates; Phytic Acid; Phytochemicals; Phytoestrogens; Tannins; Vegetables
PubMed: 32987890
DOI: 10.3390/nu12102929 -
American Journal of Physiology. Renal... Mar 2019Dietary 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... (Review)
Review
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. Large epidemiological cohort studies have demonstrated that urinary oxalate excretion is a continuous variable when indexed to stone risk. Thus, individuals with oxalate excretions >25 mg/day may benefit from a reduction of urinary oxalate output. The 24-h urine assessment may miss periods of transient surges in urinary oxalate excretion, which may promote stone growth and is a limitation of this analysis. In this review we describe the impact of dietary oxalate and its contribution to stone growth. To limit calcium oxalate stone growth, we advocate that patients maintain appropriate hydration, avoid oxalate-rich foods, and consume an adequate amount of calcium.
Topics: Calcium; Calcium Oxalate; Calcium, Dietary; Diet; Humans; Kidney Calculi; Oxalates
PubMed: 30566003
DOI: 10.1152/ajprenal.00373.2018 -
Nature Reviews. Nephrology Feb 2023Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on... (Review)
Review
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: Humans; Oxalates; Renal Dialysis; Kidney; Hyperoxaluria; Renal Insufficiency, Chronic; Renal Insufficiency; Homeostasis
PubMed: 36329260
DOI: 10.1038/s41581-022-00643-3 -
International Journal of Surgery... Dec 2016Nephrolithiasis is a complex disease of worldwide prevalence that is influenced by both genetic and environmental factors. About 75% of kidney stones are predominantly... (Review)
Review
Nephrolithiasis is a complex disease of worldwide prevalence that is influenced by both genetic and environmental factors. About 75% of kidney stones are predominantly composed of calcium oxalate and urinary oxalate is considered a crucial risk factor. Microorganisms may have a role in the pathogenesis and prevention of kidney stones and the involvement of the intestinal microbiome in this renal disease has been a recent area of interest. Oxalobacter formigenes is a gram negative bacteria that degrades oxalate in the gut decreasing urinary oxalate excretion. In this review, we examine the data studying the role of Oxalobacter formigenes in kidney stone disease in humans and animals, the effect of antibiotics on its colonization, and the potential role of probiotics and whole microbial communities as therapeutic interventions.
Topics: Animals; Anti-Bacterial Agents; Calcium Oxalate; Gastrointestinal Microbiome; Humans; Kidney Calculi; Oxalates; Oxalobacter formigenes; Probiotics; Risk Factors
PubMed: 27847292
DOI: 10.1016/j.ijsu.2016.11.024 -
Oxalate-induced apoptosis through ERS-ROS-NF-κB signalling pathway in renal tubular epithelial cell.Molecular Medicine (Cambridge, Mass.) Aug 2022Kidney stones are composed of approximately 70-80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this...
BACKGROUND
Kidney stones are composed of approximately 70-80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms.
METHODS
We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways.
RESULTS
We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited.
CONCLUSION
Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.
Topics: Animals; Apoptosis; Calcium Oxalate; Endoplasmic Reticulum Stress; Epithelial Cells; Kidney Calculi; Mice; NF-kappa B; Oxalates; Reactive Oxygen Species
PubMed: 35922749
DOI: 10.1186/s10020-022-00494-5 -
Nutrients Dec 2021Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although... (Review)
Review
Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.
Topics: Bone and Bones; Calcium; Dietary Supplements; Humans; Hypercalciuria; Intestines; Kidney Calculi; Minerals; Oxalates; Risk; Vitamin D; Vitamin D3 24-Hydroxylase
PubMed: 34959915
DOI: 10.3390/nu13124363 -
Clinical Chemistry and Laboratory... Nov 2015Crystalluria is a marker of urine supersaturation with substances deriving from metabolic disorders, inherited diseases or drugs. The investigation of crystalluria must... (Review)
Review
Crystalluria is a marker of urine supersaturation with substances deriving from metabolic disorders, inherited diseases or drugs. The investigation of crystalluria must be done according to a protocol which includes the delivery to the laboratory of a proper urine sample, the use of a microscope equipped with polarized light, the accurate knowledge of urine pH, and a comprehensive examination of the crystals, which is based on their identification, quantification and size measurement. For unusual crystals, infrared spectroscopy may also be needed. The main urinary crystalline categories include: calcium oxalates, calcium phosphates, uric acids and urates, struvite, aminoacids (cystine), purines (2,8-dihydroxyadenine and xanthine) and drugs (e.g. sulfamethoxazole, amoxycillin, ceftriaxone, atazanavir). The investigation of crystalluria is a cheap and valuable tool for the detection and the monitoring of inherited and acquired diseases associated with urinary stone formation or renal function impairment - either acute or chronic - due to intrarenal crystal precipitation.
Topics: Biomarkers; Calcium Oxalate; Calcium Phosphates; Crystallization; Humans; Metabolic Diseases; Microscopy, Polarization; Uric Acid; Urinalysis; Urinary Calculi
PubMed: 26509782
DOI: 10.1515/cclm-2015-0860 -
American Journal of Kidney Diseases :... Feb 2023Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates...
RATIONALE & OBJECTIVE
Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.
STUDY DESIGN
Phase 3, open-label, single-arm trial.
SETTING & PARTICIPANTS
Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m (if age ≥12 months) or increased serum creatinine level (if age <12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.
INTERVENTION
Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.
OUTCOME
Primary end point: percent change in POx from baseline to month 6 (cohort A; not receiving hemodialysis at enrollment) and percent change in predialysis POx from baseline to month 6 (cohort B; receiving hemodialysis at enrollment). Pharmacodynamic secondary end points: percent change in POx area under the curve between dialysis sessions (cohort B only); absolute change in POx; percent and absolute change in spot urinary oxalate-creatinine ratio; and 24-hour urinary oxalate adjusted for body surface area.
RESULTS
All patients (N = 21; 43% female; 76% White) completed the 6-month primary analysis period. Median age at consent was 8 (range, 0-59) years. For the primary end point, least-squares mean reductions in POx were 33.3% (95% CI, -15.2% to 81.8%) in cohort A (n = 6) and 42.4% (95% CI, 34.2%-50.7%) in cohort B (n = 15). Improvements were also observed in all pharmacodynamic secondary end points. Most adverse events were mild or moderate. No patient discontinued treatment or withdrew from the study. The most commonly reported lumasiran-related adverse events were injection-site reactions, all of which were mild and transient.
LIMITATIONS
Single-arm study without placebo control.
CONCLUSIONS
Lumasiran resulted in substantial reductions in POx with acceptable safety in patients with PH1 who have advanced kidney disease, supporting its efficacy and safety in this patient population.
FUNDING
Alnylam Pharmaceuticals.
TRIAL REGISTRATION
Registered at ClinicalTrials.gov with study number NCT04152200 and at EudraCT with study number 2019-001346-17.
PLAIN-LANGUAGE SUMMARY
Primary hyperoxaluria type 1 (PH1) is a rare genetic disease characterized by excessive hepatic oxalate production that frequently causes kidney failure. Lumasiran is an RNA interference therapeutic that is administered subcutaneously for the treatment of PH1. Lumasiran has been shown to reduce oxalate levels in the urine and plasma of patients with PH1 who have relatively preserved kidney function. In the ILLUMINATE-C study, the efficacy and safety of lumasiran were evaluated in patients with PH1 and advanced kidney disease, including a cohort of patients undergoing hemodialysis. During the 6-month primary analysis period, lumasiran resulted in substantial reductions in plasma oxalate with acceptable safety in patients with PH1 complicated by advanced kidney disease.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Young Adult; Hyperoxaluria; Hyperoxaluria, Primary; Kidney Diseases; Oxalates
PubMed: 35843439
DOI: 10.1053/j.ajkd.2022.05.012 -
Molecular Medicine Reports Aug 2022The present study aimed to evaluate the role and mechanism of ferrostatin‑1 (Fer‑1) in oxalate (Ox)‑induced renal tubular epithelial cell injury, fibrosis, and...
The present study aimed to evaluate the role and mechanism of ferrostatin‑1 (Fer‑1) in oxalate (Ox)‑induced renal tubular epithelial cell injury, fibrosis, and calcium oxalate (CaOx) stone formation. A CaOx model in mice kidneys was established via intraperitoneal injection of 80 mg/kg glyoxylic acid for 14 days. The mice were randomly divided into three groups (n=6), namely, the control (Con), the CaOx group, and the CaOx + Fer‑1 group. Cultured human renal tubular epithelial cells (HK‑2 cells) were randomly divided into three groups (n=3), namely, the control (Con), the Ox group, and the Ox + Fer‑1 group. The levels of heme oxygenase 1 (HO‑1), superoxide dismutase 2 (SOD2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11) were assessed by immunofluorescence and western blot analysis. Renal tubular injury and apoptosis were evaluated by H&E and TUNEL staining. Kidney interstitial fibrosis was evaluated by Masson and Sirius red staining, and the levels of E‑cadherin, vimentin and α‑SMA were detected by immunofluorescence or western blot analysis. Mitochondrial structure was observed using a transmission electron microscope. The levels of reactive oxygen species (ROS) were determined by flow cytometry and CaOx stone formation was evaluated by von Kossa staining. The results revealed that in comparison with the Con group, mitochondrial injury under glyoxylic acid treatment was observed by TEM. The expression of GPX4 and SLC7A11 in the CaOx and Ox groups was downregulated (P<0.05), whereas the expression of HO‑1 and SOD2 was upregulated (P<0.05). Renal tissue damage, apoptosis of renal tubular epithelial cells, and interstitial fibrosis were increased in the CaOx and Ox groups (P<0.05). In comparison with the CaOx or Ox group, the expression of GPX4 and SLC7A11 in the CaOx + Fer‑1 or Ox + Fer‑1 group was upregulated (P<0.05), whereas that of HO‑1 and SOD2 was downregulated (P<0.05). Renal tissue damage, apoptosis of renal tubular epithelial cells and interstitial fibrosis were decreased following Fer‑1 treatment (P<0.05). The ROS level was also decreased following Fer‑1 treatment. Moreover, CaOx stone formation was decreased in the CaOx + Fer‑1 group (P<0.05). In conclusion, Fer‑1 alleviated Ox‑induced renal tubular epithelial cell injury, fibrosis, and CaOx stone formation by inhibiting ferroptosis.
Topics: Animals; Calcium Oxalate; Cyclohexylamines; Epithelial Cells; Ferroptosis; Fibrosis; Kidney; Mice; Oxalates; Phenylenediamines; Reactive Oxygen Species
PubMed: 35703358
DOI: 10.3892/mmr.2022.12772 -
Drugs Dec 2023Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for... (Review)
Review
Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for the treatment of primary hyperoxaluria (PH). It reduces oxalate overproduction by inhibiting the expression of the hepatic lactate dehydrogenase (LDH) enzyme. Nedosiran received its first approval on 29 September 2023 in the USA to lower urinary oxalate levels in children aged ≥ 9 years and adults with PH type 1 (PH1) and relatively preserved kidney function [e.g. estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m]. This article summarizes the milestones in the development of nedosiran leading to this first approval for PH1.
Topics: Child; Adult; Humans; Hyperoxaluria, Primary; Oxalates; Lactate Dehydrogenases; RNA, Small Interfering
PubMed: 38060091
DOI: 10.1007/s40265-023-01976-4