Calcium Oxalate Kidney Stones Research Articles

Large-scale identification of calcium oxalate stone inhibitory proteins in normal human urine

Recent evidence has shown that proteins in normal human urine can inhibit calcium oxalate (CaOx) kidney stone formation. Herein, we performed fast protein liquid chromatography (FPLC) to fractionate normal human urinary proteins using anion-exchange (DEAE) and size-exclusion (Superdex 200) materials. FPLC fractions (F1-F15) were examined by CaOx crystallization, growth, aggregation and crystal-cell adhesion assays. The fractions with potent inhibitory activities against CaOx crystals were then subjected to mass spectrometric protein identification. The data revealed that 13 of 15 fractions showed inhibitory activities in at least one crystal assay. Integrating CaOx inhibitory scores demonstrated that F6, F7 and F8 had the most potent inhibitory activities. NanoLC-ESI-Qq-TOF MS/MS identified 105, 93 and 53 proteins in F6, F7 and F8, respectively. Among them, 60 were found in at least two fractions and/or listed among known inhibitors with solid experimental evidence in the StoneMod database (https://www.stonemod.org). Interestingly, 10 of these 60 potential inhibitors have been reported with lower urinary levels in CaOx stone formers compared with healthy (non-stone) individuals, strengthening their roles as potent CaOx stone inhibitors. Our study provides the largest dataset of potential CaOx stone inhibitory proteins that will be useful for further elucidations of stone-forming mechanisms and ultimately for therapeutic/preventive 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.

Corn Silk Polysaccharide Reduces the Risk of Kidney Stone Formation by Reducing Oxidative Stress and Inhibiting COM Crystal Adhesion and Aggregation.

HK-2 cells were damaged by 100 nm COM crystals to build an injury model. The cells were protected by CSPs with -COOH contents of 3.92% (CSP0) and 16.38% (CCSP3), respectively. The changes in the biochemical indexes of HK-2 cells and the difference in adhesion amount and aggregation degree of nano-COM on the cell surface before and after CSP protection were detected. CSP0 and CCSP3 protection can obviously inhibit HK-2 cell damage caused by nano-COM crystals, restore cytoskeleton morphology, reduce intracellular ROS level, inhibit phosphoserine eversion, restore the polarity of the mitochondrial membrane potential, normalize the cell cycle process, and reduce the expression of adhesion molecules, OPN, Annexin A1, HSP90, HAS3, and CD44 on the cell surface. Finally, the adhesion and aggregation of nano-COM crystals on the cell surface were effectively inhibited. The carboxymethylated CSP3 exhibited a higher protective effect on cells than the original CSP0, and cell viability was further improved with the increase in polysaccharide concentration. CSPs can protect HK-2 cells from calcium oxalate crystal damage and effectively reduce the adhesion and aggregation of nano-COM crystals on the cell surface, which is conducive to inhibiting the formation of calcium oxalate kidney stones.

The impact of crystal phase transition on the hardness and structure of kidney stones

Calcium oxalate kidney stones, the most prevalent type of kidney stones, undergo a multi-step process of crystal nucleation, growth, aggregation, and secondary transition. The secondary transition has been rather overlooked, and thus, the effects on the disease and the underlying mechanism remain unclear. Here, we show, by periodic micro-CT images of human kidney stones in an ex vivo incubation experiment, that the growth of porous aggregates of calcium oxalate dihydrate (COD) crystals triggers the hardening of the kidney stones that causes difficulty in lithotripsy of kidney stone disease in the secondary transition. This hardening was caused by the internal nucleation and growth of precise calcium oxalate monohydrate (COM) crystals from isolated urine in which the calcium oxalate concentrations decreased by the growth of COD in closed grain boundaries of COD aggregate kidney stones. Reducing the calcium oxalate concentrations in urine is regarded as a typical approach for avoiding the recurrence. However, our results revealed that the decrease of the concentrations in closed microenvironments conversely promotes the transition of the COD aggregates into hard COM aggregates. We anticipate that the suppression of the secondary transition has the potential to manage the deterioration of kidney stone disease.

Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions

IntroductionHyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through its oxalate-degrading enzyme activity. In this cross-sectional study, we leverage multi-omics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. MethodsPatients diagnosed with Type I Primary Hyperoxaluria (PH), Enteric Hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic and metatranscriptomic data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha- and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. Metatranscriptomic-based network analysis identified the most interactive bacterial network in PH patients. EH patients had a decreased abundance of multiple major oxalate degraders. ConclusionThe composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.

Antiurolithiatic effects of Cassia fistula Lin. fruit extracts on ethylene glycol-induced nephrolithiasis in rats.

Urinary stones are a growing disease that results from pathological biomineralization. Cassia fistula Lin. is traditionally used to treat urinary stones. However, no scientific evidence is available to prove its antilithiatic effect. This study evaluates the antilithiatic potential of aqueous and ethanolic extract of Cassia fistula Lin. fruit (Cff) against calcium oxalate kidney stones. Forty-two male Wistar rats were divided into seven groups (n = 6/group): Group I (control), Group II (rats treated with ethylene glycol and ammonium chloride developed nephrolithiasis after 28 days), Group III (lithiatic rats receiving distilled water for 30 days), Group IV and V (lithiatic rats receiving aqueous extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively) and Group VI and VII (lithiatic rats receiving ethanolic extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively). Some parameters of urine and serum, and also renal oxidative stress and histopathology were used to determine the antilithiatic effect of aqueous and ethanolic extract of Cff. Therefore, the types of extracts of Cff improved abnormal levels of urine, serum, and renal oxidative stress and histopathology parameters. This antilithiatic effect of aqueous and ethanolic extracts of Cff, can be attributed to the anti-crystallization and antioxidant properties of the extracts and the ability to improve urine and serum biochemistry. RESEARCH HIGHLIGHTS: Ethylene glycol and ammonium chloride-induced urolithiasis, aggregation of calcium oxalate deposits, increase of some urinary and serum parameters, relative kidney weight, kidney size and MDA activity, decrease of some urinary parameters, relative body weight and SOD activity. Aqueous and ethanolic extracts of Cassia fistula Lin. lead to the treatment of urolithic rats by decreasing levels of urinary oxalate, phosphate, urea, serum urea, uric acid, creatinine, calcium, phosphate, MDA, kidney weight and kidney size, increasing levels of urinary calcium, creatinine, magnesium, citrate, body weight and SOD activity in the kidney, eliminating CaOx deposition (esp. ethanolic extract).

GRHPR gene variations in Iraqi patients infected with calcium oxalate kidney stones

The alterations in glyoxylate reductase and hydroxy-pyruvate reductase concentrations in the sera and the genetic alterations associated with calcium oxalate kidney stones in Iraqi patients were not studied previously so this study aimed to focus on these points. This study included 80 subjects; they were 50 patients with calcium oxalate stones compared to 30 apparently healthy controls. Biochemical investigations for kidney functions (creatinine, urea, and uric acid), were performed on the sera of both groups. Also, complete blood count, random blood sugar, and blood group tests. Furthermore, urine had been collected for General Urine Examination to visualize oxalate crystals in the urine of the patient. Also, the GRHPR enzyme concentration was measured by ELISA for both groups. The DNA was isolated from whole blood and the target DNA was amplified by PCR then the pathogenic mutations at c.295C>T (rs119490108), c.165G>A (rs180177314) and c.904C>T (p. Arg302Cys) rs180177322 were investigated by direct sequencing of the product, and then the results were analyzed. This study found that the concentration of the enzyme in the controls (4.78 ± 1.06 mg/dl) was significantly higher than its concentration in the patients (0.411 ± 0.02mg/dl). The pathogenic mutations were not found in both studied groups, but other positions were found polymorphic; at exon 4 the rs2768659 (A>G), rs1294628807 (G>A) and rs2736664 (C>T), at exon 6: c.579A>G (p. Ala193=) rs309458 and c.494-68A>G rs309459 and at exon 9 c.*146A>G rs1057507. In conclusion, this study found that calcium oxalate stones were associated with decrease GRHPR enzyme concentration in the patients compared to the control group which may be caused by mutations or epigenetics masking of the gene expression.

Size-Dependent Cytotoxicity, Adhesion, and Endocytosis of Micro-/Nano-hydroxyapatite Crystals in HK-2 Cells.

Nano-hydroxyapatite (nano-HAP) is often used as a crystal nest to induce calcium oxalate (CaOx) kidney stone formation, but the mechanism of interaction between HAP crystals of different properties and renal tubular epithelial cells remains unclear. In this study, the adhesion and endocytosis of HAP crystals with sizes of 40 nm, 70 nm, 1 μm, and 2 μm (HAP-40 nm, HAP-70 nm, HAP-1 μm, and HAP-2 μm, respectively) to human renal proximal tubular epithelial cells (HK-2) were comparatively studied. The results showed that HAP crystals of all sizes promoted the expression of osteopontin and hyaluronic acid on the cell surface, destroyed the integrity of the lysosomes, and induced the apoptosis and necrosis of cells. Nano-HAP crystals had a higher specific surface area, a smaller contact angle, a higher surface energy, and a lower Zeta potential than those of micro-HAP. Therefore, the abilities of HK-2 cells to adhere to and endocytose nano-HAP crystals were greater than their abilities to do the same for micro-HAP crystals. The order of the endocytosed crystals was as follows: HAP-40 nm > HAP-70 nm > HAP-1 μm > HAP-2 μm. The endocytosed HAP crystals entered the lysosomes. The more crystal endocytosis and adhesion there is, the more toxic it is to HK-2 cells. The results of this study showed that nanosized HAP crystals greatly promoted the formation of kidney stones than micrometer-sized HAP crystals.

Role of Flavonoids in the Treatment of Urolithiasis: A Challenging Herbal Approach

A common condition that puts a huge financial and morbidity burden is kidney stones. Throughout the past 20 years, the frequency of urolithiasis has increased; 5 to 15 % of people globally are affected. Calcium oxalate (CaOx) kidney stones, which form in the renal surfaces, are the most prevalent variety. Several physicochemical processes of urinary stone constituents within tubular cells lead to the complex process of stone generation. Obese people are known to be at an increased risk of developing stones. Nephrolithiasis in women is becoming more common because of metabolic syndrome. Recent years have seen a significant change in the detection and initial treatment of urolithiasis. Calcium oxalate renal stones are the most typical type of stone proclaimed in India. Since medicinal herbs are safer, more efficient, more acceptable culturally, and have fewer side effects than produced pharmaceuticals, they have been used for treatment for millennia. Patients are recommended to follow a low-fat diet and take herbal remedies in addition to fibre from naturally occurring plants. Flavonoids are a type of plant polyphenol that has been linked to several health benefits. Recent research has revealed that plant flavonoids can significantly reduce the formation of kidney stones in vitro and in vivo, which correlates with their anti-inflammatory, antioxidant, diuretic, antibacterial, and other beneficial actions. Thus, the flavonoids or extracts of flavonoid-rich plants associated with anti-urolithiasis activity were evaluated. This article emphasises the use of flavonoid-containing plants or herbs and synthetic medications to cure kidney stones. The epidemiology, mechanism of action, pathophysiology, synthetic and natural treatments for kidney stone development, and ways to reduce stone risks are all covered in this review article.

Distinguishing characteristics of pediatric patients with primary hyperoxaluria type 1 in PEDSnet

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inborn error of metabolism that causes oxalate deposition, leading to recurrent calcium oxalate kidney stones, chronic kidney disease and systemic oxalosis, which produces a broad range of serious life-threatening complications. Patients with PH1 have delayed diagnosis due to the rarity of the disease and the overlap with early-onset kidney stone disease not due to primary hyperoxaluria. The objective of this study was to determine the clinical features of individuals <21 years of age with PH1 that precede its diagnosis. We hypothesized that a parsimonious set of features could be identified that differentiate patients with PH1 from patients with non-primary hyperoxaluria-associated causes of early-onset kidney stone disease. We determined the association between clinical characteristics and PH1 diagnosis in a case-control study conducted between 2009 and 2021 in PEDSnet, a clinical research network of eight US pediatric health systems. Each patient with genetically confirmed PH1 was matched by sex and PEDSnet institution to up to 4 control patients with kidney stones without PH of any type. We obtained patient characteristics and diagnostic test results occurring before to less than 6 months after study entrance from a centralized database query and from manual chart review. Differences were examined using standardized differences and multivariable regression. The study sample included 37 patients with PH1 and 147 controls. Patients with PH1 were younger at diagnosis (median age of 3 vs 13.5 years); 75% of children with PH1 were less than 8 years-old. Patients with PH1 were more likely to have combinations of nephrocalcinosis on ultrasound or CT (43% vs 3%), lower eGFR at diagnosis (median=52mL/min/1.73m2 vs 114mL/min/1.73m2), and have normal mobility. Patients with PH1 had higher proportion of calcium oxalate monohydrate kidney stones than controls (median=100% vs 10%). There were no differences in diagnosis of failure to thrive, stone size, or echocardiography results. Children with PH1 are characterized by presentation before adolescence, nephrocalcinosis, decreased eGFR at diagnosis, and calcium oxalate monohydrate stone composition. If externally validated, these characteristics could facilitate earlier diagnosis and treatment of children with PH1.

Oxalate disrupts monocyte and macrophage cellular function via Interleukin-10 and mitochondrial reactive oxygen species (ROS) signaling

Oxalate is a small compound found in certain plant-derived foods and is a major component of calcium oxalate (CaOx) kidney stones. Individuals that consume oxalate enriched meals have an increased risk of forming urinary crystals, which are precursors to CaOx kidney stones. We previously reported that a single dietary oxalate load induces nanocrystalluria and reduces monocyte cellular bioenergetics in healthy adults. The purpose of this study was to extend these investigations to identify specific oxalate-mediated mechanisms in monocytes and macrophages. We performed RNA-Sequencing analysis on monocytes isolated from healthy subjects exposed to a high oxalate (8 mmol) dietary load. RNA-sequencing revealed 1,198 genes were altered and Ingenuity Pathway Analysis demonstrated modifications in several pathways including Interleukin-10 (IL-10) anti-inflammatory cytokine signaling, mitochondrial metabolism and function, oxalic acid downstream signaling, and autophagy. Based on these findings, we hypothesized that oxalate induces mitochondrial and lysosomal dysfunction in monocytes and macrophages via IL-10 and reactive oxygen species (ROS) signaling which can be reversed with exogenous IL-10 or Mitoquinone (MitoQ; a mitochondrial targeted antioxidant). We exposed monocytes and macrophages to oxalate in an in-vitro setting which caused oxidative stress, a decline in IL-10 cytokine levels, mitochondrial and lysosomal dysfunction, and impaired autophagy in both cell types. Administration of exogenous IL-10 and MitoQ attenuated these responses. These findings suggest that oxalate impairs metabolism and immune response via IL-10 signaling and mitochondrial ROS generation in both monocytes and macrophages which can be potentially limited or reversed. Future studies will examine the benefits of these therapies on CaOx crystal formation and growth in vivo.

FKBP5 deficiency attenuates calcium oxalate kidney stone formation by suppressing cell-crystal adhesion, apoptosis and macrophage M1 polarization via inhibition of NF-κB signaling.

Surgical crushing of stones alone has not addressed the increasing prevalence of kidney stones. A promising strategy is to tackle the kidney damage and crystal aggregation inherent in kidney stones with the appropriate therapeutic target. FKBP prolyl isomerase 5 (FKBP5) is a potential predictor of kidney injury, but its status in calcium oxalate (CaOx) kidney stones is not clear. This study attempted to elucidate the role and mechanism of FKBP5 in CaOx kidney stones. Lentivirus and adeno-associated virus were used to control FKBP5 expression in a CaOx kidney stone model. Transcriptomic sequencing and immunological assays were used to analyze the mechanism of FKBP5 deficiency in CaOx kidney stones. The results showed that FKBP5 deficiency reduced renal tubular epithelial cells (RTEC) apoptosis and promoted cell proliferation by downregulating BOK expression. It also attenuated cell-crystal adhesion by downregulating the expression of CDH4. In addition, it inhibited M1 polarization and chemotaxis of macrophages by suppressing CXCL10 expression in RTEC. Moreover, the above therapeutic effects were exerted by inhibiting the activation of NF-κB signaling. Finally, in vivo experiments showed that FKBP5 deficiency attenuated stone aggregation and kidney injury in mice. In conclusion, this study reveals that FKBP5 deficiency attenuates cell-crystal adhesion, reduces apoptosis, promotes cell proliferation, and inhibits macrophage M1 polarization and chemotaxis by inhibiting NF-κB signaling. This provides a potential therapeutic target for CaOx kidney stones.

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.

Boosting inhibition performance of natural polyphenols for the prevention of calcium oxalate kidney stones through synergistic cooperativity

Binary drug combination usually targets different pathways to achieve cooperative therapy, but the exploitation of synergistic cooperativity between crystal growth modifiers that bind to the same site for preventing pathological biomineralization has yet to be realized. Here, we report that the binary inhibitor combinations of citrate with natural polyphenols can boost the inhibitory efficacy of calcium oxalate monohydrate crystallization, a primary component of kidney stones, up to four-fold greater than citrate alone. A combination of experimental and simulation techniques shows a strong synergy of four citrate-polyphenol inhibitor pairs on suppressing calcium oxalate monohydrate growth with minimal amounts of inhibitor, resulting from the reduction of growth kinetic constant paralleled with suppressing the crystallization driving force. Further, the inhibitor pairs demonstrated both in vitro and in vivo synergistic reductions of crystal-cell interactions, renal calcium oxalate deposition, and kidney injury, collectively presenting an effective therapeutic strategy for preventing calcium oxalate stones by boosting the inhibition efficacy of potent inhibitor pairs.

Spectroscopic investigation of phase transformation of calcium oxalate dehydrates (renal calculi) using acidic Bryophyllum pinnatom powder

Urolithiasis is one of most common renal disorders, characterized by the formation of kidney stones (renal calculi) through the crystallization process within the urinary system. The frequently observed renal calculi are calcium oxalate renal calculi and treatment is done by shock wave method or lithotripsy which is harmful for other cells of the internal system. The objective of this work was to evaluate in vitro diagnosis of calcium oxalate kidney stones in the aqueous solution of Bryophyllum pinnatum. The B. pinnatum powder was mixed in apple cider vinegar and lemon juice separately to make solution 1 and 2 respectively. Apple cider vinegar and lemon juice were used as solvents due to their acidic and body compatible nature. Two surgically removed stones was dipped in solution 1 and 2. After two weeks, kidney stone of weight 2.7 g is completely dissolved in solution 2 while a considerable weight reduction of other kidney stone has been observed in solution 1. Fourier transform infrared (FTIR) spectroscopy results show the presence of two strong absorption peaks at 610 and 912 (cm−1) in both solutions after dissolution of urinary stones are related to calcium oxalate dehydrate (COD). Raman spectra further confirm the dissolution of COD in solution having Raman shifts at 504 and 910 (cm−1). Cluster formation and aggregation of particles has been observed in scanning electron microscopy images. This in vitro study proves that a mixture of Bryophyllum pinnatum powder and lemon juice is a best remedy to remove kidney stones.

Diet in Different Calcium Oxalate Kidney Stones.

Diet can be a helpful tool to enhance the quality of urine and lower the likelihood and recurrence of kidney stones. This study set out to identify the foods and nutrients that are associated with each type of calcium oxalate kidney stone formation. A single-center, cross-sectional study was conducted. Between 2018 and 2021, a sample of 90 cases (13 cases with papillary COM, 27 with non-papillary COM, and 50 with COD kidney stones), as well as a control group of 50 people, were chosen. A food intake frequency questionnaire was completed by the study's participants, and the results were compared between groups. Additionally, a comparison of the 24 h urine analysis between stone groups was made. Processed food and meat derivatives were linked to COM papillary calculi (OR = 1.051, p = 0.032 and OR = 1.013, p = 0.012, respectively). Consuming enough calcium may offer protection against non-papillary COM stones (OR = 0.997; p = 0.002). Similarly, dairy product consumption was linked to COD calculi (OR = 1.005, p = 0.001). In conclusion, a diet high in animal items may increase the risk of developing papillary COM stones. Consuming calcium may be preventive against non-papillary COM calculi, and dairy product consumption may be a risk factor for COD stones.

Risk factors and predictors of urogenous sepsis after percutaneous nephrolithotomy for idiopathic calcium oxalate nephrolithiasis.

The aim of this study was to use bioinformatics approaches to screen and identify the key genes of idiopathic calcium oxalate nephrolithiasis, and explore its potential molecular mechanism. The GSE73680 kidney stone data set was downloaded from the Gene Expression Omnibus (GEO). R software (The R Foundation for Statistical Computing) was used to screen differentially expressed genes. GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze related genes interacting with crucial genes, and a protein-protein interaction (PPI) network was constructed. The differential genes were then subjected to the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. The clinical data of 156 patients who received percutaneous nephrolithotomy (PCNL) therapy at our facility between January 2013 and December 2017 were retrospectively analyzed. The various parameters associated with postoperative urogenous sepsis were identified using multivariable logistic regression analysis. The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 (NOD2). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways. The clinical parameter of patients who participated in the study, including preoperative urinary white blood cell (WBC) count, preoperative urinary nitrite, stone diameter, operation time, WBC count, and WBC D values, were statistically different between the systemic inflammatory response syndrome (SIRS) group and the urosepsis group. According to multivariate logistic regression analysis, the preoperative urine nitrite, calculus diameter, blood WBC, and NOD2 expression 3 hours after surgery were all independently associated with the urosepsis development. Preoperative urinary nitrite positive status, postoperative WBC count ≥2.98×109/L 3 hours after operation, stone diameter >6 cm, and low expression of NOD2 in renal papillary tissue are more likely to cause the urinary source of idiopathic calcium oxalate nephrolithiasis after PCNL urogenous sepsis. These parameters also offer a viable treatment paradigm for the perioperative management of PCNL in treating idiopathic calcium oxalate kidney stones.

Evidence for Solution-Mediated Phase Transitions in Kidney Stones: Phase Transition Exacerbates Kidney Stone Disease

In this study, we investigated calcium oxalate (CaOx) kidney stones and showed direct evidence of the solution-mediated phase transition of calcium oxalate dihydrate (COD; the metastable phase) to calcium oxalate monohydrate (COM; the stable phase). We examined the crystal phases, crystal textures, and protein distributions within thin sections of calcium oxalate kidney stones. Observation with a polarized-light microscope showed that the outline of the mosaic texture, in which COM crystals are assembled in a mosaic pattern, roughly coincides with COD’s crystallographically stable face angles. Microfocus X-ray CT measurement captured the intermediate process of the phase transition, starting inside the COD single crystal and gradually transforming to COM crystals. In addition, the distribution of osteopontin and prothrombin fragment-1, common proteins contained in urine and visualized by multicolor fluorescence immunostaining, showed no apparent striations inside the COM single crystals with the mosaic texture, although the striation is apparent inside the COD single crystals. This is probably because the phase transition of mosaic-like COM occurred in a semiclosed system inside the COD single crystal, so the effect of periodic (day–night, seasonal, etc.) urinary protein concentration changes was small. On the other hand, striations were visible in concentrically laminated COM. This indicated that concentrically laminated COM formed in response to the changes in urinary protein concentrations. From the above, we conclude that the COD single crystals and the concentrically laminated COM seen in CaOx stones are primary structures, and the mosaic COM is a secondary structure that is a pseudomorph formed by the solution-mediated phase transition from COD single crystals.

MP05-14 ENHANCED POPCORNING USING POLYANIONIC SOLUTIONS AS IRRIGATION

You have accessJournal of UrologyCME1 Apr 2023MP05-14 ENHANCED POPCORNING USING POLYANIONIC SOLUTIONS AS IRRIGATION Daniel Wong, Alex Shiang, Connor McCormick, Adam Ostergar, Henry Lai, and Kenneth Sands Daniel WongDaniel Wong More articles by this author , Alex ShiangAlex Shiang More articles by this author , Connor McCormickConnor McCormick More articles by this author , Adam OstergarAdam Ostergar More articles by this author , Henry LaiHenry Lai More articles by this author , and Kenneth SandsKenneth Sands More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003216.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The goal of popcorning or pop-dusting is to reduce stone fragments to submillimeter size, allowing spontaneous passage through the urinary tract. Polyanionic compounds can dissolve human calcium oxalate kidney stones. We explore the novel application of polyanionic solutions to enhance popcorning efficiency. METHODS: BegoStones with matching size and mass were treated in a 12 mm test tube calyceal model with a 60 W TFL (SOLTIVE, Olympus). 200 mm fiber was introduced into our model calyx through a flexible ureteroscope and positioned 1-2 mm from the stones. Stones were treated at 1.0 J × 40 Hz for 4 minutes with irrigation at 30 ml/min. We compared sodium chloride (NaCl), sodium citrate (Citrate), sodium hexametaphosphate (HMP), and sodium EDTA (EDTA) solutions. The osmolality of all solutions was matched to 0.9% NaCl. The pH for solutions of NaCl, EDTA, HMP, and Citrate was 6.0, 8.3, 6.7, and 8.6 respectively. After treatment, stones were passed through a 1 mm sieve and remaining fragments weighed. The primary outcome was residual stone mass >1 mm. RESULTS: The average remaining stone mass >1 mm after 17 observations with NaCl irrigation was 27.8% (±10.0%). After 15 observations with HMP, Citrate, and EDTA irrigation, the average remaining stone mass >1 mm was 28.9% (±13.4%), 17.5% (±10.5%), and 9.8% (±5.7%) respectively (Figure 1). HMP had no significant effect on residual stone burden compared with NaCl. There was a 37% reduction in residual stone mass when using Citrate compared with NaCl (p=0.008). Using EDTA reduced residual stone mass by 65% compared with NaCl (p<0.001). CONCLUSIONS: Citrate and EDTA show promising results for enhancing the efficacy of popcorning in this in vitro model. Further testing will be required to determine effectiveness on different stone types and safety on urothelium in short duration. Source of Funding: Midwest Stone Institute © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e48 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Wong More articles by this author Alex Shiang More articles by this author Connor McCormick More articles by this author Adam Ostergar More articles by this author Henry Lai More articles by this author Kenneth Sands More articles by this author Expand All Advertisement PDF downloadLoading ...

Ferroptosis in calcium oxalate kidney stone formation and the possible regulatory mechanism of ANKRD1

The objective of this study was to explore the role of ferroptosis in the formation of calcium oxalate (CaOx) kidney stones and the regulatory mechanism of the ankyrin repeat domain 1 (ANKRD1) gene. The study found that the Nrf2/HO-1 and p53/SLC7A11 signaling pathways were activated in the kidney stone model group, and the expression of the ferroptosis marker proteins SLC7A11 and GPX4 was significantly reduced, while the expression of ACSL4 was significantly increased. The expression of the iron transport-related proteins CP and TF increased significantly, and Fe2+ accumulated in the cell. The expression of HMGB1 increased significantly. In addition, the level of intracellular oxidative stress was increased. The gene with the most significant difference caused by CaOx crystals in HK-2 cells was ANKRD1. Silencing or overexpression of ANKRD1 by lentiviral infection technology regulated the expression of the p53/SLC7A11 signaling pathway, which regulated the ferroptosis induced by CaOx crystals. In conclusion, CaOx crystals can mediate ferroptosis through the Nrf2/HO-1 and p53/SLC7A11 pathways, thereby weakening the resistance of HK-2 cells to oxidative stress and other unfavorable factors, enhancing cell damage, and increasing crystal adhesion and CaOx crystal deposition in the kidney. ANKRD1 participates in the formation and development of CaOx kidney stones by activating ferroptosis mediated by the p53/SLC7A11 pathway.