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.

Hair-straightening cosmetics containing glyoxylic acid induce crystalline nephropathy.

We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a "Brazilian" hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.

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.

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.

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.

Chronic Kidney Disease and Kidney Stone in a Wild Chimpanzee (Pan troglodytes verus) in Côte d'Ivoire.

An older wild female chimpanzee (Pan troglodytes) was found dead with a large calcium oxalate stone in the renal pelvis. Histopathological changes included glomerulosclerosis, interstitial nephritis and fibrosis, focal mineralization, and medial hypertrophy. Urinary albumin-creatinine-ratio showed increased values from 15 months before death. Causes of the kidney disease remain unconfirmed.

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.

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.

Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Photonic Lithotripsy: Near-Infrared Laser Activated Nanomaterials for Kidney Stone Comminution.

Near-infrared activated nanomaterials have been reported for biomedical applications ranging from photothermal tumor destruction to biofilm eradication and energy-gated drug delivery. However, the focus so far has been on soft tissues, and little is known about energy delivery to hard tissues, which have thousand-fold higher mechanical strength. We present photonic lithotripsy with carbon and gold nanomaterials for fragmenting human kidney stones. The efficacy of stone comminution is dependent on the size and photonic properties of the nanomaterials. Surface restructuring and decomposition of calcium oxalate to calcium carbonate support the contribution of photothermal energy to stone failure. Photonic lithotripsy has several advantages over current laser lithotripsy, including low operating power, noncontact laser operation (distances of at least 10 mm), and ability to break all common stones. Our observations can inspire the development of rapid, minimally invasive techniques for kidney stone treatment and extrapolate to other hard tissues such as enamel and bone.

Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence.

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone.

Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.

The Anti-urolithiatic effect of the roots of Saussurea costus (falc) Lipsch agonist ethylene glycol and magnesium oxide induced urolithiasis in rats.

Phytotherapy, which involves the use of plant extracts and natural compounds for medicinal purposes, is indeed a promising alternative for managing urinary lithiasis. Many plants have been studied for their potential to prevent and treat kidney stones, and they may offer a more natural and potentially less harmful approach compared to conventional treatments. Additionally, phytotherapy may be more cost-effective. The aim of the present study was to investigate the antilithic potential of extracts and essential oils of Saussurea costus (Falc) Lipsch in two in vivo models, one on ethylene glycol-induced calcium oxalate crystal formation and the other to assess the effects of these extracts on magnesium oxide-induced struvite crystal formation. The experiment involved the administration of different doses of aqueous and ethanolic extracts of S. costus (200 and 400 mg/kg) and essential oils (25 and 50 mg/kg) to male Wistar rats, followed by the evaluation of various physiological, biochemical and histopathological parameters. The results demonstrated that the administration of S. costus essential oils and extracts had significant effects on the rats, influencing body weight, urine volume, crystal deposition, cytobacteriological examination of urine, and serum biochemical parameters. Histopathological examinations revealed varying impacts on the kidneys and livers of the treated rats. The findings suggest that S. costus extracts and essential oils may hold promise in inhibiting calcium oxalate crystal formation in vivo and influencing various physiological and biochemical parameters in rats. Overall, the 200 mg/kg ethanolic extract of S. costus demonstrated antilithiatic efficacy, did not exhibit signs of toxicity and reduced the number of crystals in the kidneys. Furthermore, the study did not find a significant effect on reducing struvite crystals.

Safety and efficacy of a polyherbal formulation from traditional Persian medicine in patients with calcium kidney stones: A randomized, double-blinded clinical trial.

Background: 10%-15% of the world's population suffers from kidney stones. Nearly 50% increase was observed in diagnosing and treating nephrolithiasis in the last decades. Effective medical treatment for the disease is not yet well established. Moreover, there is an increasing global demand to manage diseases using complementary and alternative medicine. This study aimed to formulate and assess the safety and efficacy of a multi-ingredient formulation from traditional Persian medicine (TPM) known as Mofatet powder in patients suffering from calcium kidney stones. Materials and Methods: The aqueous extract of Mofatet powder was prepared, freeze-dried, and formulated as capsules. 26 patients in the drug group and 25 patients in the placebo group used 500 mg capsules of the drug/placebo twice daily for 5 weeks. Ultrasonography/kidney, ureter and bladder imaging, urine analysis, and biochemical parameters were evaluated before and after the intervention. Results: The imaging results showed a 60.73% decrease (P < 0.001) in stone size in the drug group. Moreover, the urinary calcium decreased (P = 0.02) and the urinary magnesium increased (P < 0.001) in the drug group. No remarkable changes were observed in the placebo group in these parameters. No significant effect was observed in aspartate transaminase, alanine transaminase, serum creatinine, and blood urea nitrogen levels in none of the groups. Conclusion: This study suggests that Mofatet powder was effective in reducing calcium kidney stones size with no potential nephro/hepatotoxicity. After confirming these results in larger clinical trials with longer duration, this formulation can be considered a treatment for nephrolithiasis.