Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.

The pathogenesis of renal calcium-oxalate (CaOx) stones is complex and influenced by various metabolic factors. In parallel, palmitic acid (PA) has been identified as an upregulated lipid metabolite in the urine and serum of patients with renal CaOx stones via untargeted metabolomics. Thus, this study aimed to mechanistically assess whether PA is involved in stone formation. Lipidomics analysis of PA-treated renal tubular epithelial cells compared with the control samples revealed that α-linoleic acid and α-linolenic acid were desaturated and elongated, resulting in the formation of downstream polyunsaturated fatty acids (PUFAs). In correlation, the levels of fatty acid desaturase 1 and 2 (FADS1 and FADS2) and peroxisome proliferator-activated receptor α (PPARα) in these cells treated with PA were increased relative to the control levels, suggesting that PA-induced upregulation of PPARα, which in turn upregulated these two enzymes, forming the observed PUFAs. Lipid peroxidation occurred in these downstream PUFAs under oxidative stress and Fenton Reaction. Furthermore, transcriptomics analysis revealed significant changes in the expression levels of ferroptosis-related genes in PA-treated renal tubular epithelial cells, induced by PUFA peroxides. In addition, phosphatidyl ethanolamine binding protein 1 (PEBP1) formed a complex with 15-lipoxygenase (15-LO) to exacerbate PUFA peroxidation under protein kinase C ζ (PKC ζ) phosphorylation, and PKC ζ was activated by phosphatidic acid derived from PA. In conclusion, this study found that the formation of renal CaOx stones is promoted by ferroptosis of renal tubular epithelial cells resulting from PA-induced dysregulation of PUFA and phosphatidic acid metabolism, and PA can promote the renal adhesion and deposition of CaOx crystals by injuring renal tubular epithelial cells, consequently upregulating adhesion molecules. Accordingly, this study provides a new theoretical basis for understanding the correlation between fatty acid metabolism and the formation of renal CaOx stones, offering potential targets for clinical applications.

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

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

PURPOSE: Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. These conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease, and kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in chronic kidney disease when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1. The goal of this narrative review is to address the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. MATERIALS AND METHODS: We collated our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. RESULTS: In our experience, increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. CONCLUSIONS: Alongside biochemical assessments, more widespread genetic testing may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

Ascorbate degradation: pathways, products, and possibilities.

A role for l-ascorbate as the precursor of several plant compounds adds to its already broad metabolic utility. There are many examples of plant species in which oxalate and l-threonate are formed from l-ascorbate breakdown, and a number of roles have been proposed for this: structural, physiological, and biochemical. On the other hand, the synthesis of l-tartrate from l-ascorbate remains limited to a very few species, amongst which we must be grateful to count the domesticated grapevine Vitis vinifera and its relatives on which wine production is based. Pathways for the degradation of ascorbate were first proposed ~50 years ago and have formed the basis of more recent biochemical and molecular analyses. The present review seeks to summarize some of these findings and to propose opportunities for future research.

Mechanism of oxalate decarboxylase Oxd_S12 from Bacillus velezensis BvZ45-1 in defence against cotton verticillium wilt.

Verticillium wilt, a soilborne vascular disease caused by Verticillium dahliae, strongly affects cotton yield and quality. In this study, an isolated rhizosphere bacterium, designated Bacillus velezensis BvZ45-1, exhibited >46% biocontrol efficacy against cotton verticillium wilt under greenhouse and field conditions. Moreover, through crude protein extraction and mass spectrometry analyses, we found many antifungal compounds present in the crude protein extract of BvZ45-1. The purified oxalate decarboxylase Odx_S12 from BvZ45-1 inhibited the growth of V. dahliae Vd080 by reducing the spore yield, causing mycelia to rupture, spore morphology changes, cell membrane rupture, and cell death. Subsequently, overexpression of Odx_S12 in Arabidopsis significantly improved plant resistance to V. dahliae. Through studies of the resistance mechanism of Odx_S12, V. dahliae was shown to produce oxalic acid (OA), which has a toxic effect on Arabidopsis leaves. Odx_S12 overexpression reduced Arabidopsis OA content, enhanced tolerance to OA, and improved resistance to verticillium wilt. Transcriptomics and quantitative real-time PCR analysis revealed that Odx_S12 promoted a reactive oxygen species burst and a salicylic acid- and abscisic acid-mediated defence response in Arabidopsis. In summary, this study not only identified B. velezensis BvZ45-1 as an efficient biological control agent, but also identified the resistance gene Odx_S12 as a candidate for cotton breeding against verticillium wilt.

The synergistic effect of multiple organic macromolecules on the formation of calcium oxalate raphides of Musa spp.

Needle-like calcium oxalate crystals called raphides are unique structures in the plant kingdom. Multiple biomacromolecules work together in the regulatory and transportation pathways to form raphides; however, the mechanism by which this occurs remains unknown. Using banana (Musa spp.), this study combined in vivo methods including confocal microscopy, transmission electron microscopy, and Q Exactive mass spectrometry to identify the main biomolecules, such as vesicles, together with the compositions of lipids and proteins in the crystal chamber, which is the membrane compartment that surrounds each raphide during its formation. Simulations of the vesicle transportation process and the synthesis of elongated calcium oxalate crystals in vitro were then conducted, and the results suggested that the vesicles carrying amorphous calcium oxalate and proteins embedded in raphides are transported along actin filaments. These vesicles subsequently fuse with the crystal chamber, utilizing the proteins embedded in the raphides as a template for the final formation of the structure. Our findings contribute to the fundamental understanding of the regulation of the diverse biomacromolecules that are crucial for raphide formation. Moreover, the implications of these findings extend to other fields such as materials science, and particularly the synthesis of functionalized materials.

The catalytic action of human d-lactate dehydrogenase is severely inhibited by oxalate and is impaired by mutations triggering d-lactate acidosis.

d-lactate dehydrogenases are known to be expressed by prokaryotes and by eukaryotic invertebrates, and over the years the functional and structural features of some bacterial representatives of this enzyme ensemble have been investigated quite in detail. Remarkably, a human gene coding for a putative d-lactate dehydrogenase (DLDH) was identified and characterized, disclosing the occurrence of alternative splicing of its primary transcript. This translates into the expression of two human DLDH (hDLDH) isoforms, the molecular mass of which is expected to differ by 2.7 kDa. However, no information on these two hDLDH isoforms is available at the protein level. Here we report on the catalytic action of these enzymes, along with a first analysis of their structural features. In particular, we show that hDLDH is strictly stereospecific, with the larger isoform (hDLDH-1) featuring higher activity at the expense of d-lactate when compared to its smaller counterpart (hDLDH-2). Furthermore, we found that hDLDH is strongly inhibited by oxalate, as indicated by a Ki equal to 1.2 µM for this dicarboxylic acid. Structurally speaking, hDLDH-1 and hDLDH-2 were determined, by means of gel filtration and dynamic light scattering experiments, to be a hexamer and a tetramer, respectively. Moreover, in agreement with previous studies performed with human mitochondria, we identified FAD as the cofactor of hDLDH, and we report here a model of FAD binding by the human d-lactate dehydrogenase. Interestingly, the mutations W323C and T412 M negatively affect the activity of hDLDH, most likely by impairing the enzyme electron-acceptor site.

Mitochondrial dysfunction and NLRP3 inflammasome: key players in kidney stone formation.

The mitochondrion serves as a critical intracellular organelle, engaging in essential roles in the regulation of energy production, oxidative stress management, calcium homeostasis, and apoptosis. One such disease that has been particularly associated with these functions is kidney stone disease (KSD), specifically calcium oxalate (CaOx). It is underpinned by oxidative stress and tissue inflammation. Recent studies have shed light on the vital involvement of mitochondrial dysfunction, the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome, endoplasmic reticulum stress and subsequent cell death in CaOx crystal retention and aggregation. These processes are pivotal in the pathogenesis of kidney stone formation. This review focuses on the pivotal roles of mitochondria in renal cell functions and provides an overview of the intricate interconnectedness between mitochondrial dysfunction and NLRP3 inflammasome activation in the context of KSD. It is essential to recognise the utmost significance of gaining a comprehensive understanding of the mechanisms that safeguard mitochondrial function and regulate the NLRP3 inflammasome. Such knowledge carries significant scientific implications and opens up promising avenues for the development of innovative strategies to prevent the formation of kidney stones.

Exploring optimal settings for safe and effective thulium fibre laser lithotripsy in a kidney model.

OBJECTIVES: To explore the optimal laser settings and treatment strategies for thulium fibre laser (TFL) lithotripsy, namely, those with the highest treatment efficiency, lowest thermal injury risk, and shortest procedure time. MATERIALS AND METHODS: An in vitro kidney model was used to assess the efficacy of TFL lithotripsy in the upper calyx. Stone ablation experiments were performed on BegoStone phantoms at different combinations of pulse energy (EP ) and frequency (F) to determine the optimal settings. Temperature changes and thermal injury risks were monitored using embedded thermocouples. Experiments were also performed on calcium oxalate monohydrate (COM) stones to validate the optimal settings. RESULTS: High EP /low F settings demonstrated superior treatment efficiency compared to low EP /high F settings using the same power. Specifically, 0.8 J/12 Hz was the optimal setting, resulting in a twofold increase in treatment efficiency, a 39% reduction in energy expenditure per unit of ablated stone mass, a 35% reduction in residual fragments, and a 36% reduction in total procedure time compared to the 0.2 J/50 Hz setting for COM stones. Thermal injury risk assessment indicated that 10 W power settings with high EP /low F combinations remained below the threshold for tissue injury, while higher power settings (>10 W) consistently exceeded the safety threshold. CONCLUSIONS: Our findings suggest that high EP /low F settings, such as 0.8 J/12 Hz, are optimal for TFL lithotripsy in the treatment of COM stones. These settings demonstrated significantly improved treatment efficiency with reduced residual fragments compared to conventional settings while keeping the thermal dose below the injury threshold. This study highlights the importance of using the high EP /low F combination with low power settings, which maximizes treatment efficiency and minimizes potential thermal injury. Further studies are warranted to determine the optimal settings for TFL for treating kidney stones with different compositions.

SGLT-2 inhibitors and nephrolithiasis risk: a meta-analysis.

BACKGROUND AND AIM: Sodium-glucose cotransporter (SGLT)-2 inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight. In addition to the beneficial effects on renal functions, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT-2 inhibitor therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options. MATERIALS AND METHODS: We have performed a literature search through multiple databases, including PubMed, Ovid/Medline, Web of Science, Scopus, and Cochrane Library. We have followed the systematic review and meta-analysis guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.We have included a total of 11 635 698 patients who experienced nephrolithiasis from six clinical trials to conduct this meta-analysis study. In the pooled analysis, nephrolithiasis occurred in 1,27% of patients from the SGLT2i group (n = 739 197), compared to 1,56% of patients (n = 10 896 501) from the control arm (active control, placebo or no therapy). RESULTS: We have included a total of 11 635 698 participants who experienced nephrolithiasis from a total of six clinical studies with nephrolithiasis rates of 1,27% in the SGLT2i group (n = 739 197), compared to 1,56% in the control arm (n = 10 896 501). SGLT-2 inhibitor therapy has been associated with a lower risk for nephrolithiasis compared to placebo (OR 0.61, 95% CI, 0.53-0.70, p < 0.00001) or active therapy such as glucagon-like peptide 1 and dipeptidyl peptidase-IV inhibitors (OR 0.66, 95% CI, 0.47-0.93, p = 0.02). CONCLUSION: We have demonstrated a lower risk of nephrolithiasis risk with SGLT-2 inhibitor therapy compared to placebo or active control. Potential underlying mechanisms include osmotic diuresis leading to a reduction in the concentration of lithogenic substances, anti-inflammatory and anti-fibrotic effects, and an increase in urine pH. There is a clear need for future large-scale randomized clinical trials evaluating such associations for better understanding.

Comparison of metabolic parameters between pure-uric acid and mixed-uric acid kidney stone formers.

PURPOSE: We seek to compare clinical and 24-h urine parameters between pure-uric acid (UA) and UA-CaOx stone formers in our practice and explore how any differences in metabolic profiles could suggest different prevention strategies between the two groups. METHODS: We retrospectively reviewed patients with either pure- or mixed-UA nephrolithiasis from 2020 to 2023 at a tertiary care center. We included patients with a 24-h urine collection and a stone analysis detecting any amount of UA. Patients were organized into two cohorts: (1) those with 100% UA stones and (2) < 100% UA stones. Differences in demographic characteristics were compared between pure-UA and UA-CaOx stone formers. Twenty-four hour urine metabolic parameters as well as metabolic abnormalities were compared between the pure-uric acid and mixed-uric acid groups. RESULTS: We identified 33 pure-UA patients and 33 mixed-UA patients. Patient demographics were similar between the groups (Table 1). Pure- and mixed-UA patients had a similar incidence of metabolic syndrome, diabetes, history of stones, and stone burden. Table 1 Demographic and baseline characteristics among pure- and mixed-uric acid stone formers Pure-uric acid stones (n = 33) Mixed-uric acid stones (n = 33) p-value Median age [IQR] 63.00 [58.00-72.50] 63.00 [53.50-68.00] 0.339 Median BMI [IQR] 28.79 [25.81-33.07] 27.96 [25.81-29.55] 0.534 Gender, n (%) 1.000  Male 21 (63.6) 21 (63.6)  Female 12 (36.4) 12 (36.4) Metabolic syndrome, n (%) 17 (51.5) 16 (48.5) 0.806 Diabetes, n (%) 13 (39.4) 12 (36.4) 0.800 History of stones, n (%) 23 (69.7) 22 (66.7) 0.792 Median total stone burden, mm [IQR] 12.00 [6.00-26.50] 13.00 [7.05-20.00] 0.995 Median serum uric acid, mg/dL [IQR] 6.20 [4.80-7.15] 5.90 [4.98-6.89] 0.582 IQR Interquartile range BMI Body Mass Index n number We found the pure-UA cohort to have 24-h lower urine volume (1.53 vs. 1.96 L/day, p = 0.045) and citrate levels (286 vs. 457 mg/day, p = 0.036). UA-CaOx stone formers had higher urinary calcium levels (144 vs. 68 mg/day, p = 0.003), higher urinary oxalate levels (38 vs. 30 mg/day, p = 0.017), and higher median urinary calcium oxalate super-saturation (3.97 vs. 3.06, p = 0.047). CONCLUSIONS: Pure-UA kidney stone formers have different urinary metabolic parameters when compared with UA-CaOx stone formers, thus requiring different and tailored medical management.

Glyoxylate reductase: Definitive identification in human liver mitochondria, its importance for the compartment-specific detoxification of glyoxylate.

Glyoxylate is a key metabolite generated from various precursor substrates in different subcellular compartments including mitochondria, peroxisomes, and the cytosol. The fact that glyoxylate is a good substrate for the ubiquitously expressed enzyme lactate dehydrogenase (LDH) requires the presence of efficient glyoxylate detoxification systems to avoid the formation of oxalate. Furthermore, this detoxification needs to be compartment-specific since LDH is actively present in multiple subcellular compartments including peroxisomes, mitochondria, and the cytosol. Whereas the identity of these protection systems has been established for both peroxisomes and the cytosol as concluded from the deficiency of alanine glyoxylate aminotransferase (AGT) in primary hyperoxaluria type 1 (PH1) and glyoxylate reductase (GR) in PH2, the glyoxylate protection system in mitochondria has remained less well defined. In this manuscript, we show that the enzyme glyoxylate reductase has a bimodal distribution in human embryonic kidney (HEK293), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cells and more importantly, in human liver, and is actively present in both the mitochondrial and cytosolic compartments. We conclude that the metabolism of glyoxylate in humans requires the complicated interaction between different subcellular compartments within the cell and discuss the implications for the different primary hyperoxalurias.

Oxalate Nephropathy After Kidney Transplantation: Risk Factors and Outcomes of Two Phenotypes.

Describing risk factors and outcomes in kidney transplant recipients with oxalate nephropathy (ON) may help elucidate the pathogenesis and guide treatment strategies. We used a large single-center database to identify patients with ON and categorized them into delayed graft function with ON (DGF-ON) and late ON. Incidence density sampling was used to select controls. A total of 37 ON cases were diagnosed between 1/2011 and 1/2021. DGF-ON (n = 13) was diagnosed in 1.05% of the DGF population. Pancreatic atrophy on imaging (36.4% vs. 2.9%, p = 0.002) and gastric bypass history (7.7% vs. 0%; p = 0.06) were more common in DGF-ON than with controls with DGF requiring biopsy but without evidence of ON. DGF-ON was not associated with worse graft survival (p = 0.98) or death-censored graft survival (p = 0.48). Late ON (n = 24) was diagnosed after a mean of 78.2 months. Late ON patients were older (mean age 55.1 vs. 48.4 years; p = 0.02), more likely to be women (61.7% vs. 37.5%; p = 0.03), have gastric bypass history (8.3% vs. 0.8%; p = 0.02) and pancreatic atrophy on imaging (38.9% vs. 13.3%; p = 0.02). Late ON was associated with an increased risk of graft failure (HR 2.0; p = 0.07) and death-censored graft loss (HR 2.5; p = 0.10). We describe two phenotypes of ON after kidney transplantation: DGF-ON and late ON. Our study is the first to our knowledge to evaluate DGF-ON with DGF controls without ON. Although limited by small sample size, DGF-ON was not associated with adverse outcomes when compared with controls. Late ON predicted worse allograft outcomes.

Chemical characterization and speciation of the soluble fraction of Arctic PM10.

The chemical composition of the soluble fraction of atmospheric particulate matter (PM) and how these components can combine with each other to form different species affect the chemistry of the aqueous phase dispersed in the atmosphere: raindrops, clouds, fog, and ice particles. The study was focused on the analysis of the soluble fraction of Arctic PM10 samples collected at Ny-Ålesund (Svalbard Islands, Norwegian Arctic) during the year 2012. The concentration values of Na+, K+, NH4+, Ca2+, Mg2+, Mn2+, Cu2+, Zn2+, Fe3+, Al3+, Cl-, NO2-, NO3-, SO42-, PO43-, formate, acetate, malonate, and oxalate in the water-soluble fraction of PM10 were determined by atomic spectroscopy and ion chromatography. Speciation models were applied to define the major species that would occur in aqueous solution as a function of pH (2-10). The model highlights that (i) the main cations such as Na+, K+, Mg2+, and Ca2+ occur in the form of aquoions in the whole investigated pH range; (ii) Cu2+, Zn2+, and, in particular, Fe3+ and Al3+ are mostly present in their hydrolytic forms; and (iii) Al3+, Fe3+, and Cu2+ form solid hydrolytic species that precipitate at pH values slightly higher than neutrality. These latter metals show interesting interactions with oxalate and sulfate ions, too. The speciation models were also calculated considering the seasonal variability of the concentration of the components and at higher concentration levels than those found in water PM extracts, to better simulate concentrations actually found in the atmospheric aqueous phase. The results highlight the role of oxalate as the main organic ligand in solution.

Localized calcium oxalate crystals in primary cutaneous aspergillosis.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.

Seminal papers in urology: urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study : Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A. urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. The Journal of urology. 1996 Mar;155(3):839 - 43.

Kidney stones, a persistent urological condition, continue to affect people globally. In this critical review, we examine the work of Borghi et al. who evaluated patients with idiopathic stone formation and randomised 99 patients to increased water intake (≥ 2 L/day) and 100 patients to usual care in a 5-year randomized controlled trial. The study examined baseline urine volume in individuals with idiopathic calcium stones, recurrence rates, and relevant biochemical factors. The study found reduced recurrence rate (12.1% vs. 27% (p = 0.008)), and time to recurrence with increased water intake (38.7 ± 13.2 months) vs. (25 ± 16.4 months) (p = 0.016). These findings inform clinical practice, contributing to the guideline recommendations that kidney stone patients should aim for fluid intake of at least 2.5 L per day to prevent stone recurrence.

Oxalate nephropathy after pancreaticoduodenectomy: a case report.

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.

Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007-2018.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones. METHODS: We performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders. RESULTS: The multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10-1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15-1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09-1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13-1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06-1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02-1.54, P = 0.033) in Model 3. CONCLUSIONS: Our study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.

MAGNESIUM SUPPLEMENTATION INCREASES URINE MAGNESIUM AND CITRATE IN STONE FORMERS WITH HYPOMAGNESURIA.

OBJECTIVES: To compare the effects of magnesium repletion by a foods-alone approach or by magnesium supplementation on urinary magnesium and citrate excretion in patients with urine magnesium <70 mg/day. METHODS: We reviewed medical records of patients in our stone prevention practice who were advised to start a magnesium supplement (Sup), 250-500 mg/d, or increase dietary magnesium consumption. We included adults with 24h UMg <70 mg, those who received magnesium recommendations (corroborated by the dietitian's clinical notes), and those with a follow-up 24h urine collection ≤18 months. Urine results were assessed by group. RESULTS: Groups [No Sup (n=74) and Sup (n=56)] were not different for age, gender, stone history, malabsorption, or other clinical indices. All patients raised UMg (53 to 69 and 47 to 87 mg/d for No Sup and Sup, respectively); however, the increase was significantly higher in the Sup group. Moreover, while 88% of Sup patients achieved UMg ≥70 mg/d, only 58% in the No Sup group did so. Within-group increases in urine citrate were significant only in the Sup group. CONCLUSION: Among patients with low UMg, both higher consumption from foods and magnesium supplementation significantly increased UMg. However, those who supplemented were significantly more likely to reach or exceed UMg 70 mg/d and achieved higher mean UMg. The change in urine citrate was significant only among those in the Sup group.

Solid-State Synthesis of Liquorice-Stabilized Copper-Based Nanoparticles: Structural and Catalytic Studies.

A large-scale quantity of copper oxalate nanoparticles were successfully obtained via a facile and green solid-state chemical reaction. Copper oxalate nanoparticles were obtained by ball-milling between copper chloride, Liquorice (Glycyrrhiza glabra), and ascorbic acid at ambient conditions. The size and morphology of copper oxalate nanoparticles powder were studied by transmission and scanning electron microscopy. The prepared nanoparticles were semi-spherical in shape and ranged from 5 to 15 nm in size. UV/Vis spectroscopy, Fourier transforms infrared spectroscopy, and X-ray photoelectron spectroscopy measurements were carried out to characterize the prepared samples. Copper oxalate nanoparticles were evaluated as a catalyst in the catalytic degradation of 4-nitrophenol, bromophenol blue, reactive yellow, and a mixture of the three pollutants. The present study combined solid-state reaction and green requirements for the mass production of nanomaterials. The proposed reaction is performed in simple steps, inexpensive, low energy consuming, solvent-free, and minimizes the emission of secondary wastes.