Calcium Oxalate Stone Formation Research Articles

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100nm calcium oxalate monohydrate for 24h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators.Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44.The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis.

Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

Role of Rosmarinus officinalis Aqueous Extract in Relieving the Complications Associated with Ethylene Glycol-induced Urolithiasis in Male Rats

Background:: Rosmarinus officinalis is considered one of the famous plants from ancient times for its therapeutic ability in many diseases, such as headache, spasms, brain disorders, and some pathological conditions associated with toxicity cases in the liver and kidneys. Aim:: The current research has aimed, for the first time, to evaluate anti-urolithiatic effect of Rosmarinus officinalis aqueous extract (RMAE) on calcium oxalate stones formation in male rats and its possible therapeutic mechanisms of action. Evaluation of the polyphenols and flavonoid content in the extract was also performed. Methods:: A calcium oxalate nephrolithiasis case was established in rats by adding ethylene glycol (1%) to the rats' daily drinking water for a duration of one month. Treatment was achieved by oral co-administration of RMAE to rats administrated ethylene glycol. Results:: Phytochemical results showed that LC/MS-MS analysis led to the identification of 37 compounds in the phytoconstituent profile of RMAE. The biochemical results revealed significant improvement in serum kidney functions (urea, creatinine, and uric acid) in addition to restoring the calcium x phosphorous product and parathyroid hormone (PTH) levels in the plant-treated group compared to the non-treated one. The data have been supported by the significant decrease in lactate dehydrogenase enzyme (LDH) expression in the liver tissues, reflecting the decrease in oxalate synthesis in the liver compared to the non-treated group. Kidneys' histological examinations showed the absence of oxalate crystals in the treated group and the immunohistochemical findings of osteopontin (OPN) protein revealed the impact of RMAE on OPN expression in kidney tissues. Improvements in the femur bone fractures and the parathyroid gland in the treated group were also noticed during microscopic examinations. Conclusion:: The anti-lithiatic effect of the extract was attributed to its influence on serum phosphate, serum PTH, and OPN levels in kidney tissues and decreasing synthesis of LDH in liver tissues in addition to the prevention of secondary disease incidences, such as secondary hyperparathyroidism and cardiovascular diseases. On the other hand, the plant's considerable content of phenolics and flavonoids has been found to play a role in controlling kidney stone progression episodes.

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.

Contrasting Response of Urine Stone Risk to Medical Treatment in Calcium Oxalate versus Calcium Phosphate Stone Formers.

Randomized controlled trials have shown that both thiazide diuretics and potassium citrate (K-Cit) can prevent calcium stone recurrence, but most participants formed calcium oxalate stones (CaOx). While thiazides are expected to lower stone risk for calcium phosphate (CaP) stones, the effect of K-Cit on risk for CaP stones is unclear. To study the impact of common calcium stones treatments, we analyzed the 24-hour urines of CaOx and CaP stone formers (SF) by 4 treatment types: Lifestyle, K-Cit, Thiazide, or Both medications. Patients treated with thiazides reduced urine calcium in both CaOx (M = -74.4, SD = 94.6 mg/day) and CaP SF (M = -102, SD = 99.7 mg/day), while those on K-Cit had no change in urine calcium. Among CaOx SF, urine citrate rose in patients administered K-Cit with or without thiazide, but citrate did not rise significantly in CaP SF. Urine pH rose in all CaOx SF, but among CaP SF only rose in patients receiving K-Cit. CaOx supersaturation (SS) decreased in all patients who received Thiazide, and decreased among CaOx SF treated with K-Cit. CaP SS decreased in both CaOx SF (M = -0.46, SD = 0.86) and CaP SF (M = -0.76, SD = 0.85) treated with Thiazide except CaOx SF who received Both. Patients treated with K-Cit alone increased CaP SS in CaOx SF (M = 0.25, SD = 0.79). Patients treated with Thiazide lowered urine calcium and SS in both stone groups. Patients treated with K-Cit had no significant changes in urine calcium and had a decrease in CaOx SS in CaOx SF. The study raises questions about the best preventive treatment for patients with CaP stones and suggests that K-Cit may not confer the same benefits on CaP SF as it does on CaOx SF.

Intestinal Oxalate Absorption, Enteric Hyperoxaluria, and Risk of Urinary Stone Formation in Patients with Crohn's Disease.

Nephrolithiasis is a common urologic manifestation of Crohn's disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn's disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [13C2]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn's disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [13C2]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Exosomes from miR-23 Overexpressing Stromal Cells Suppress M1 Macrophage and Inhibit Calcium Oxalate Deposition in Hyperoxaluria Rat Model.

To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model. An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes. The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3'-untranslated region (3'-UTR) and miR-23 was confirmed by the dual-luciferase reporter assay. In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model.

Differential Effects of Thiazide, Alkali, or Both on Urine Determinants of Stone Risk in Calcium Oxalate (CaOx) and Calcium Phosphate (CaP) Stone Formers

Differential Effects of Thiazide, Alkali, or Both on Urine Determinants of Stone Risk in Calcium Oxalate (CaOx) and Calcium Phosphate (CaP) Stone Formers

Potential role of glutathione S‑transferase M1 gene polymorphism in kidney calcium oxalate stone formation.

The purpose of this study was to look into the effects of glutathione S-transferase M1 (GSTM1) gene polymorphism on the formation of kidney calcium oxalate stones. A total of 159 patients with kidney calcium oxalate stones were included in this study as a case group. One hundred and three healthy individuals were included in the control group. The age, gender, and levels of calcium (Ca), uric acid (UA), creatinine (Cr), and urinary creatinine (Ucr) are tracked. Peripheral blood samples are used to perform a polymerase chain reaction to identify the glutathione S-transferase (GST) gene polymorphism (PCR). A commercial kit was used in this study to measure the levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T-AOC), and 8-hydroxydeoxyguanosine (8-OHdG) in peripheral blood. There was no difference in age or gender distribution between the case and control groups (P > 0.05). The Cr, Ucr, Ca, UA, 8-OHdG, MDA, NO, and T-AOC in the case group were significantly higher than those in the control group (P < 0.001). The Hardy-Weinberg genetic equilibrium test showed no difference between the case group (P = 0.23) and the control group (P = 0.09). In the case group, the 8-OHdG and NO in GSTM1 null genotype were significantly higher than those in GSTM1 genotype(P < 0.05), but there was no significant difference in MDA and T-AOC (P > 0.05). Multivariate regression analysis showed that the GSTM1 null genotype was positively correlated with 8-OHdG (P < 0.001) and NO (P < 0.001). GSTM1 gene polymorphism might be a detecting risk factor for kidney calcium oxalate stone formation. ChiCTR2100051300.

Oxalate‑induced renal pyroptotic injury and crystal formation mediated by NLRP3‑GSDMD signaling invitro and invivo.

Calcium oxalate kidney stone has become an urgent issue due to its high incidence and recurrence rate. Thus, it is necessary to explore for mechanisms of calcium oxalate stones formation. Previous studies demonstrated that oxalate crystals could induce the activation of nucleotide‑binding domain and leucine‑rich repeat‑containing family pyrin domain‑containing 3 (NLRP3) inflammasome and change the renal tubular epithelium adhesion. However, the type and molecular mechanism of NLRP3 inflammasome‑mediated calcium oxalate stones formation still need to be further investigated. In the present study, it was confirmed that the NLRP3‑gasdermin D (GSDMD) signaling was involved in oxalate‑induced cell injury invitro and invivo. Inhibition of reactive oxygen species production could effectively prevent the NLRP3 inflammasome formation in oxalate‑treated HK‑2cells. NLRP3 gene silence could inhibit the DNA damage and cellular membrane injury of HK‑2cells treated with oxalate. The ultrastructural changes of several organelles and particular structures, similar to typical cell pyroptosis, were observed in oxalate‑stimulated HK‑2cells. NLRP3 gene silence could antagonize the oxalate‑induced injury and ultrastructure changes. Additionally, NSA (GSDMD inhibitor) could prevent the oxalate‑induced injury of membrane integrity in HK‑2cells. Moreover, oxalate crystals were significantly decreased in GSDMD‑/‑ mice compared with wild‑type mice with glyoxylic acid. Together, NLRP3‑GSDMD pathway was involved in the oxalate‑induced pyroptotic injury in HK‑2cells. GSDMD and its cleavage form GSDMD‑N played an important role in the oxalate‑induced renal cell injury and oxalate calcium crystals formation invitro and invivo. This provided a new target for prevention and treatment of oxalate nephropathy and oxalate calcium stones.

Urine pH and Citrate as Predictors of Calcium Phosphate Stone Formation.

Urinary parameters including urine pH and citrate are recognized as critical in the pathophysiology of calcium-based stones. The factors contributing to variation in these parameters between calcium oxalate and calcium phosphate stone formers are however not well understood. In this study using readily available laboratory data, we explore these differences to delineate the odds of forming calcium phosphate (CaP) versus calcium oxalate (CaOx) stones. In this single-center retrospective study, we compared serum and urinary parameters between adult CaP stone formers (SF), CaOx SF, and non-stone formers (NSF). Urine pH was higher and urine citrate lower in CaP SF compared to same-sex CaOx SF and NSF. In CaP SF, higher urine pH and lower citrate were independent of markers of dietary acid intake and gastrointestinal alkali absorption, suggesting abnormal renal citrate handling and urinary alkali excretion. In a multivariable model, urine pH and urine citrate were most discriminatory between CaP SF and CaOx SF (Receiver Operating Characteristic Area Under the Curve of 0.73 and 0.65 respectively). An increase in urine pH by 0.35, a decrease in urine citrate by 220 mg/day, a doubling of urine calcium, and female sex all independently doubled the risk of CaP compared to CaOx. High urine pH and hypocitraturia are two clinical parameters that distinguish the urine phenotype of CaP SF from CaOx SF. The alkalinuria is due to intrinsic differences in the kidney independent of intestinal alkali absorption and is accentuated in the female sex.

Comparison of two software programs used to determine the relative supersaturation of urine ions.

Relative supersaturation (RSS) values for urine crystals are a measure of the risk of urinary stone formation and have been shown to be lowered in foods shown to aid in the management of urolithiasis. In order to calculate RSS in pets, computer programs have been developed to calculate RSS and aid in the understanding of stone formation in veterinary medicine. However, some older programs have not been updated for use in animals, and the specific coefficients used are not publically available. One of the first RSS programs was developed in BASIC computer language and published in 1985 which was called EQUIL2. The EQUIL2 program was updated to a compiled version compatible with a PC platform. However, the formulas could not be read or altered. This study evaluates a new program with known coefficients to the original EQUIL2 program. The RSS values of the two programs were compared through a t-test, calculating the r2 from correlation analysis, Lin's concordance correlation coefficient, and by a Bland-Altman analysis of outputs from the two programs using urine samples from healthy dogs and cats. Our results show that for both magnesium ammonium phosphate (struvite) and calcium oxalate, the RSS values of the original program could be calculated from the new programs RSS values. Although the actual RSS values were different (as might be expected through the use of the updated coefficients and different thermodynamic stability constants in the calculations) the results were highly correlated, finding elevations and reductions in RSS proportionally in the same urine samples. The current work creates a foundation for using the modernized program to calculate RSS and provides a shared method for understanding the risk of struvite and calcium oxalate stone formation.

Impact of body mass index on size and composition of urinary stones: a systematic review and meta-analysis.

Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.

Is hyperuricosuria really a risk factor for calcium oxalate stone formation?

In the seventies of the last century the term hyperuricosuric calcium oxalate (CaOx) urolithiasis has been coined. Allopurinol significantly decreased the recurrence in CaOx stone formers. Nevertheless, the role of hyperuricosuria has been questioned. Other mechanisms could have decreased the risk for recurrence. The underlying mechanisms are not clear. All these studies have been performed with only a limited number of patients. We studied n=2,480 consecutive patients with CaOx stones. For stone analysis, x-ray diffraction was used. The following parameters were examined in all patients: age, sex, body mass index (BMI), arterial blood pressure, stone episodes, diabetes mellitus; blood: creatinine, glucose, uric acid, calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate, ammonia and urea. According to the uric acid excretion (UAE), patients were divided into two groups: 1. UAE &gt; 4 mmol/d (hyperuricosuria), 2. UAE ≤ 4 mmol/d (normouricosuria). We observed significant correlations between UAE and sex, age, BMI, blood pressure, serum values of creatinine, sodium, urine volume, urine levels of calcium, citrate, urea and ammonia as well as serum calcium. No significant correlations were seen to the stone frequency (number of stone episodes), serum potassium and urine pH. In group 1 (n=741), there were 87.2% male and 12.8% female patients; in group 2 (n=1,739), the ratio was 60.6:39.4%. In the hyperuricosuric group, there were significantly more males than in the normouricosuric collective. Hyperuricosuric subjects had a higher BMI, higher blood levels of uric acid and glucose, a higher diuresis, a higher excretion of calcium, urea and ammonium, but a lower excretion of citrate than normouricosuric patients. All the other parameters did not show any significant differences. Especially the number of stone episodes was not different. We concluded that hyperuricosuria went along with many other risk factors for CaOx stone formation, but was not associated with an increased risk for recurrence. Therefore, UAE is not a prognostic marker in CaOx urolithiasis. It is unlikely that hyperuricosuria is a real risk factor for CaOx stone formation and hyperuricosuric CaOx urolithiasis is an own entity.

Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: Two birds with one stone.

Deposition of calcium oxalate (CaOx) crystals and oxidative stress-induced injury of renal tubular epithelial cell are the primary pathogenic factors of nephrolithiasis. In this study we investigated the beneficial effects of metformin hydrochloride (MH) against nephrolithiasis and explored the underlying molecular mechanism. Our results demonstrated that MH inhibited the formation of CaOx crystals and promoted the transformation of thermodynamically stable CaOx monohydrate (COM) to more unstable CaOx dihydrate (COD). MH treatment effectively ameliorated oxalate-induced oxidative injury and mitochondrial damage in renal tubular cells and reduced CaOx crystal deposition in rat kidneys. MH also attenuated oxidative stress by lowering MDA level and enhancing SOD activity in HK-2 and NRK-52E cells and in a rat model of nephrolithiasis. In both HK-2 and NRK-52E cells, COM exposure significantlylowered the expressions of HO-1 and Nrf2, which was rescued by MH treatment even in the presence of Nrf2 and HO-1 inhibitors. In rats with nephrolithiasis, MH treatment significantly rescued the down-regulation of the mRNA and protein expression of Nrf2 and HO-1 in the kidneys. These results demonstrate that MH can alleviate CaOx crystal deposition and kidney tissue injury in rats with nephrolithiasis by suppressing oxidative stress and activating the Nrf2/HO-1 signaling pathway, suggesting the potential value of MH in the treatment of nephrolithiasis.

Hormonal and molecular characterization of calcium oxalate stone formers predicting occurrence and recurrence

The purpose of the study is to investigate the role of sex hormones, androgen receptors (ARs) and miRNA/CSF-1 in occurrence and recurrence of calcium oxalate (CaOx) renal urolithiasis. In this prospective study, 74 patients with CaOx stones; stone formers group (SFG) and 40 healthy subjects; control group were compared. SFG includes both de novo and recurrent cases. Steroid sex hormone plasma assay including testosterone, free testosterone, dihydrotestosterone, estradiol, and sex hormone binding globulin was analyzed. ARs, miRNA-185-5p and CSF-1 expression were compared between the groups. SFG showed significant higher ARs and miRNA-185-5p expression (3.7 ± 1.3, 1.8 ± 0.4, respectively) than control group (1 ± 0.08 and 1 ± 0.07, respectively) (p < 0.05). However, CSF-1 expression was significantly lower in stone formers than control group (0.4 ± 0.19 vs 1 ± 0.1, respectively) (p < 0.05). No differences were detected between de novo and recurrent SFG regarding sex hormones, AR, miRNA or CSF-1 expression. Our data suggest the important role of AR, miRNA and CSF-1 signaling in human nephrolithiasis pathogenesis.

MP05-06 INDIVIDUALS' STONE COMPOSITION VARIABILITY OVER TIME: SINGLE INSTITUTION STUDY

You have accessJournal of UrologyCME1 Apr 2023MP05-06 INDIVIDUALS' STONE COMPOSITION VARIABILITY OVER TIME: SINGLE INSTITUTION STUDY Margaret A. Knoedler, Shuang Li, Ali S Antar, Stephen Y. Nakada, and Kristina L. Penniston Margaret A. KnoedlerMargaret A. Knoedler More articles by this author , Shuang LiShuang Li More articles by this author , Ali S AntarAli S Antar More articles by this author , Stephen Y. NakadaStephen Y. Nakada More articles by this author , and Kristina L. PennistonKristina L. Penniston More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003216.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stone analysis is important for directing metabolic stone management of patients at risk for recurrent stones. In addition to results from 24 h urine collections, knowledge of stone composition serves as a pathway to diagnosis of underlying disorders. The objective of this study was to assess stone composition over time in patients with at least two composition analyses. METHODS: We retrospectively reviewed data for patients within our health system with stone composition analyses from 1997 to 2022. Patients with ≥2 analyses ≥12 months apart were identified. Stones were collected through spontaneous passage or procedures (shock wave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy). Patients’ predominant stone compositions were defined as the component ≥60% and were otherwise considered mixed. Stones that were 100% organic material were excluded from analysis. Univariate analyses (chi-square, T test) were used to compare patients’ stone analyses. RESULTS: We reviewed 4131 stone analyses and identified 338 patients with 2 or more analyses and 76 patients who had three or more analyses. Patients were 41% female and averaged 51±14 years (min-max 18-84 years) at the time of their first stone composition. Eighty-nine (26.3%) patients had a change in their predominant stone component from the first to second stone; 26 (34.2%) had a change from the first to third stone. The mean time between the first and second stone analyses was 54 months (range 12-188, median 44 months); time between the second and third stone analyses was 76 months (range 14-258, median 61 months). A small number of patients, 3.2% of all calcium oxalate stone formers, changed from predominantly calcium oxalate in the first stone analysis to calcium phosphate in the second. This was not different (p=0.84, Fisher’s exact test) than the number whose stones changed from calcium phosphate in the first stone analysis to calcium oxalate in the second (3.8%) (Figure 1). CONCLUSIONS: Patients’ stone composition demonstrated variability in repetitive analyses. Repeating stone analyses may be an important component of long term medical stone management for individual patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e45 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Margaret A. Knoedler More articles by this author Shuang Li More articles by this author Ali S Antar More articles by this author Stephen Y. Nakada More articles by this author Kristina L. Penniston More articles by this author Expand All Advertisement PDF downloadLoading ...

MP05-09 IDENTIFICATION OF ABERRANT GLYCOSYLATION OF OSTEOPONTIN ON URINARY STONE FORMATION IN UROLITHIASIS PATIENTS AND RENAL STONE FORMATION RATS

You have accessJournal of UrologyCME1 Apr 2023MP05-09 IDENTIFICATION OF ABERRANT GLYCOSYLATION OF OSTEOPONTIN ON URINARY STONE FORMATION IN UROLITHIASIS PATIENTS AND RENAL STONE FORMATION RATS Go Anan, Tohru Yoneyama, Takuo Hirose, Makoto Sato, Takefumi Mori, and Chikara Ohyama Go AnanGo Anan More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Takuo HiroseTakuo Hirose More articles by this author , Makoto SatoMakoto Sato More articles by this author , Takefumi MoriTakefumi Mori More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003216.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Osteopontin (OPN) is one of the most important components in the calcium stone matrix. However, the relationship between glycosylation of OPN and urinary stone formation remains unknown. This study aims to identify the aberrant glycosylation profile of OPN related to urolithiasis in urolithiasis patients and renal calcium oxalate stone formation rats. METHODS: We retrospectively measured urinary glycosylated OPN normalized by urinary full-length-OPN (uFL-OPN) levels in 110 urolithiasis patients and 157 healthy volunteers. Also, we used rats with ethylene glycol-induced renal stones to evaluate the aberrant glycosylation of OPN in renal tissue. The urinary full-length-OPN levels were measured using enzyme-linked immunosorbent assay and glycosylated OPN was measured using a lectin array and lectin blotting. The assays were evaluated using the area under the receiver operating characteristics curve to discriminate stone forming urolithiasis patients. RESULTS: In the retrospective cohort, urinary Gal3C-S lectin reactive- (Gal3C-S-) OPN/uFL-OPN, was significantly higher in the stone forming urolithiasis patients than in the healthy volunteers (p<0.0001), with good discrimination (AUC, 0.953), 90% sensitivity, and 92% specificity. The Lycopersicon esculentum lectin (LEL) analysis of uFL-OPN showed that uFL-OPN in stone forming urolithiasis patients had a polyLacNAc structure that was not observed in healthy volunteers. The rats study showed that the levels of LEL-reactive OPN that had a polyLacNAc structure were increased in the renal cortex, even though total OPN levels did not increase. CONCLUSIONS: The aberrant glycosylation of OPN occurs in urine of urolithiasis patients and in renal cortex of renal stone formation rats. The aberrant glycosylation of OPN might be a marker of accelerated renal stone formation. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e47 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Go Anan More articles by this author Tohru Yoneyama More articles by this author Takuo Hirose More articles by this author Makoto Sato More articles by this author Takefumi Mori More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF downloadLoading ...

Stone Formation Features in the Kidney of Residents in the South Region of Kyrgyzstan

Kidney stone disease (KSD), otherwise urolithiasis, is one of the most common and frequent diseases and occurs most often in patients of working age. With “urolithiasis” there is a metabolic disorder characterized by the presence of stones in the kidneys and urinary tract. Formation of kidney stones in residents of southern region in Kyrgyzstan has not been studied. Research objectives: determination of stone formation features in the kidney of patients in the southern region of Kyrgyzstan. Research materials and methods: a literary review of urolithiasis (KSD) of the kidneys and identification of stone formation features. Research results: kidney stone formation is a complex physical and chemical process, accompanied by growth, aggregation and retention of urinary stone in parts of tubular cells. Conclusions: formation of calcium oxalate and uric acid stones is associated with various metabolic processes in the body. Urinary calculi are formed as a result of a series of sequence of stages.

Gut microbiota-derived uremic toxins enhance calcium oxalate stone formation in vitro and in vivo

Gut microbiota-derived uremic toxins enhance calcium oxalate stone formation in vitro and in vivo