Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

OBJECTIVE: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. METHODS: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. RESULTS: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. CONCLUSION: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Purslane-induced oxalate nephropathy: case report and literature review.

BACKGROUND: The kidney is particularly vulnerable to toxins due to its abundant blood supply, active tubular reabsorption, and medullary interstitial concentration. Currently, calcium phosphate-induced and calcium oxalate-induced nephropathies are the most common crystalline nephropathies. Hyperoxaluria may lead to kidney stones and progressive kidney disease due to calcium oxalate deposition leading to oxalate nephropathy. Hyperoxaluria can be primary or secondary. Primary hyperoxaluria is an autosomal recessive disease that usually develops in childhood, whereas secondary hyperoxaluria is observed following excessive oxalate intake or reduced excretion, with no difference in age of onset. Oxalate nephropathy may be overlooked, and the diagnosis is often delayed or missed owning to the physician's inadequate awareness of its etiology and pathogenesis. Herein, we discuss the pathogenesis of hyperoxaluria with two case reports, and our report may be helpful to make appropriate treatment plans in clinical settings in the future. CASE PRESENTATION: We report two cases of acute kidney injury, which were considered to be due to oxalate nephropathy in the setting of purslane (portulaca oleracea) ingestion. The two patients were elderly and presented with oliguria, nausea, vomiting, and clinical manifestations of acute kidney injury requiring renal replacement therapy. One patient underwent an ultrasound-guided renal biopsy, which showed acute tubulointerstitial injury and partial tubular oxalate deposition. Both patients underwent hemodialysis and were discharged following improvement in creatinine levels. CONCLUSIONS: Our report illustrates two cases of acute oxalate nephropathy in the setting of high dietary consumption of purslane. If a renal biopsy shows calcium oxalate crystals and acute tubular injury, oxalate nephropathy should be considered and the secondary causes of hyperoxaluria should be eliminated.

The preventive effects of Ulva lactuca aqueous extract, ulvan polysaccharides and atorvastatin on ethylene glycol-induced hyperoxaluria.

OBJECTIVE: Kidney stones are a common complication of hyperoxaluria. The aim of this study is to investigate the protective and preventive effects of Ulva lactuca aqueous extract, ulvan polysaccharides and atorvastatin on ethylene glycol-induced hyperoxaluria. MATERIALS AND METHODS: Male Wistar rats between 110 and 145 g in weight were used in the study, Ulva lactuca aqueous extract and polysaccharides were prepared. The male albino rats were supplemented with 0.75 percent ethylene glycol (v/v) in their drinking water for six weeks to induce hyperoxaluria. Ulvan infusions (100 mg/kg body weight), ulvan polysaccharides (100 mg/kg body weight), and atorvastatin (two milligrams/kg body weight) to treat hyperoxaluric rats for four weeks (every other day) were used. Weight loss, serum creatinine, serum urea, serum uric acid, serum oxalate, kidney oxalate, kidney lipid peroxidation, and kidney DNA fragmentation and kidney histopathological studies were done. RESULTS: Weight loss, rise of serum creatinine, serum urea, serum uric acid, serum oxalate, kidney oxalate, kidney lipid peroxidation, and kidney DNA fragmentation were all shown to be prevented by the addition of atorvastatin, polysaccharides, or aqueous extract, respectively. Catalase (CAT) activity, glutathione peroxidase (GPX) activity, glutathione-S-transferase (GST) activity, and histopathological perturbations were all significantly reduced by the medicines that were studied. CONCLUSIONS: Hyperoxaluria caused by ethylene glycol may be prevented by a combination of Ulva lactuca aqueous extract, ulvan polysaccharides, and atorvastatin. A reduction in renal oxidative stress and an improvement of the antioxidant defense system may be responsible for these protective benefits. However, Ulva lactuca infusion and ulvan polysaccharides need to be studied further in humans, in order to determine their efficacy and safety.

Acetate attenuates hyperoxaluria-induced kidney injury by inhibiting macrophage infiltration via the miR-493-3p/MIF axis.

Hyperoxaluria is well known to cause renal injury and end-stage kidney disease. Previous studies suggested that acetate treatment may improve the renal function in hyperoxaluria rat model. However, its underlying mechanisms remain largely unknown. Using an ethylene glycol (EG)-induced hyperoxaluria rat model, we find the oral administration of 5% acetate reduced the elevated serum creatinine, urea, and protected against hyperoxaluria-induced renal injury and fibrosis with less infiltrated macrophages in the kidney. Treatment of acetate in renal tubular epithelial cells in vitro decrease the macrophages recruitment which might have reduced the oxalate-induced renal tubular cells injury. Mechanism dissection suggests that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of miR-493-3p by increasing H3K9 and H3K27 acetylation at its promoter region. The miR-493-3p can suppress the expression of macrophage migration inhibitory factor (MIF), thus inhibiting the macrophages recruitment and reduced oxalate-induced renal tubular cells injury. Importantly, results from the in vivo rat model also demonstrate that the effects of acetate against renal injury were weakened after blocking the miR-493-3p by antagomir treatment. Together, these results suggest that acetate treatment ameliorates the hyperoxaluria-induced renal injury via inhibiting macrophages infiltration with change of the miR-493-3p/MIF signals. Acetate could be a new therapeutic approach for the treatment of oxalate nephropathy.

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018-004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here. METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7-20.5) months). RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)). CONCLUSIONS: Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.

Anti-urolithiatic Activity of Daidzin in Ethylene Glycol-Induced Urolithiasis in Rats.

Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.

Chaga mushroom-induced oxalate nephropathy that clinically manifested as nephrotic syndrome: A case report.

RATIONALE: The Chaga mushroom (Hymenochaetaceae, Inonotus obliquus) is a fungus belonging to the Hymenochaetaceae family. It is parasitic on birch and other tree species. Chaga mushrooms are rich in various vitamins, minerals, and nutrients. Some people consider these mushrooms medicinal as they have been reported to suppress cancer progression through anti-inflammatory and antioxidant effects. However, recent studies have reported that excessive ingestion of Chaga mushrooms can cause acute oxalate nephropathy. PATIENT CONCERNS: A 69-year-old man who ingested Chaga mushroom powder (10-15 g per day) and vitamin C (500 mg per day) for the past 3 months developed acute kidney injury (AKI) with the clinical manifestations of nephrotic syndrome (NS). DIAGNOSIS: Pathological findings showed focal acute tubular injury and the deposition of calcium oxalate crystals in the tubules. Light microscopy showed interstitial fibrosis and tubular atrophy, and electron microscopy showed the effacement of the foot processes in podocytes. Based on these results, the diagnosis was acute oxalate nephropathy accompanied by minimal change disease (MCD). INTERVENTIONS: The patient's kidney function did not improve with supportive care, such as hydration and blood pressure control. Thus, we recommended hemodialysis and the administration of a high dose of steroids (intravenous hydrocortisone 500 mg twice a day for 3 days and oral prednisolone at 1 mg/kg). OUTCOMES: The patient's kidney function recovered just 1 month after the start of treatment, and the MCD was completely remitted. LESSONS: In cases of AKI with an unknown cause, it is important to closely observe the patient's medication history, and it is recommended to perform kidney biopsy. Furthermore, this study showed that active dialysis and high-dose steroid treatment can restore kidney function in patients with AKI caused by acute oxalate nephropathy with MCD.

Diet-induced oxalate nephropathy from excessive nut and seed consumption.

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.

Is There Such a Thing as "Anti-Nutrients"? A Narrative Review of Perceived Problematic Plant Compounds.

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.

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.

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression.

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3'-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca2+ groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca2+-treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression.

Future treatments for hyperoxaluria.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: In the near future, there will likely be therapies targeting both endogenous and dietary oxalate, especially in subsets of kidney stone formers.

Protective roles of trigonelline against oxalate-induced epithelial-to-mesenchymal transition in renal tubular epithelial cells: An in vitro study.

Fibrogenesis is a common feature for all types of chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the main processes involving renal fibrosis and its inhibition is considered as a preventive/therapeutic strategy for CKD. Trigonelline (TRIG), a plant alkaloid commonly found in herbs, coffee bean, soy bean and other edible food plants, has several beneficial effects on human health and has been proposed to reduce renal fibrosis but with unclear mechanisms. This study thus addressed cellular mechanism underlying the anti-fibrogenic effects of TRIG in renal tubular epithelial cells grown in vitro. EMT was successfully induced by oxalate treatment as indicated by morphological changes into spindle-shape cells, increased expression of mesenchymal proteins (fibronectin, vimentin and α-smooth muscle actin (α-SMA)), decreased expression of epithelial proteins (E-cadherin and zonula occludens-1 (ZO-1)) and increased activity of a profibrotic factor (matrix metalloproteinase-9 (MMP-9)). Interestingly, these oxalate-induced EMT features could be attenuated by TRIG pretreatment. Moreover, TRIG also prevented oxalate-induced cell migration, reactive oxygen species (ROS) overproduction, and down-regulation of Nrf-2 signaling molecule. These data indicated that TRIG could attenuate the effects of oxalate-induced EMT and thus may serve as the anti-fibrotic compound for prevention and/or treatment of CKD.

Acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency.

Oxalate kidney injury can manifest as oxalate nephropathy or nephrolithiasis and present as acute kidney injury or even as end-stage renal disease. There are several known causes for acute oxalate nephropathy; however, the combination of exocrine pancreatic insufficiency with overconsumption of vitamin C has not been described before. In this case, a man in his early 80s presented with anorexia and extreme fatigue for 1 week. He had a history of myalgic encephalomyelitis, also known as chronic fatigue syndrome, for which he took several supplements, including high doses of vitamin C. Furthermore, several years ago, he was diagnosed elsewhere with exocrine pancreatic insufficiency. On admission, acute kidney injury was diagnosed. The kidney biopsy showed oxalate nephropathy as the cause. We diagnosed acute oxalate nephropathy due to high vitamin C doses and exocrine pancreatic insufficiency. Within 14 days, his kidney function got worse and he required renal replacement therapy.

Diet-induced oxalate nephropathy.

Oxalate nephropathy is a rare condition and may be overlooked due to lack of recognition and understanding of triggers. An 81-year-old man was sent to nephrologist because of significantly increased creatinine (1.5-1.9 mg/dL) noted for 3 months. He had well-controlled diabetes but no history of kidney disease. He had no chronic diarrhoea or intestinal surgery. He was a health-minded individual who had read extensively about benefit of antioxidants. Initial work-up was unrevealing. Within a few weeks after first visit, he developed acute symptomatic worsening kidney injury with nausea, vomiting and creatinine up to 6.8 mg/dL. Repeat examination of the urine sediment revealed casts containing calcium oxalate crystals. A deeper dietary history revealed widespread oxalate precursor consumption. A kidney biopsy confirmed oxalate nephropathy. Restriction of oxalate consumption combined with adequate hydration, oral calcium acetate resulted in partial renal recovery without need for haemodialysis.