Urinary Crystals Research Articles

Acidification and inhibition of crystals in urine for the management of peristomal skin

Presentamos el caso de un varón de 72 años diagnosticado de cáncer vesical músculo-invasivo en 2016 intervenido de cistectomía radical laparoscópica con derivación Bricker. En el seguimiento del paciente, su estomaterapeuta observa estenosis del estoma y granulomas en la piel periestomal. Este es un problema frecuente en pacientes urostomizados que suele aparecer a los 3 meses tras cirugía. Actualmente los tratamientos utilizados son fomentos de ácido acético al 50% o cauterización con nitrato de plata, ambos sin evidencia científica. Nos planteamos eliminar los granulomas y evitar futuras lesiones en la piel periestomal administrando un complemento alimenticio a base de L-metioninina para controlar el pH urinario. Materiales y métodos: Paciente que acude a consulta de nuestra estomaterapeuta al presentar estenosis de la estoma debido al acúmulo de cristales úricos, así como la aparición de granulomas en la piel periestomal. Tras varios sedimentos de orina, se observa repetidamente un pH alcalino y orina fétida. Se inicia el tratamiento con L-metionina con el objetivo de disminuir el pH, mejorando así los parámetros urinarios y la integridad de la piel periestomal. Resultados: Tres meses después del inicio del tratamiento se observa una disminución del pH urinario, una disminución del número de infecciones y una mejoría del olor de la orina y de los granulomas periestomales. Tras 2 años, el paciente mantiene íntegra la piel periestomal. Discusión: Sobre el 50% de las personas ostomizadas presentan complicaciones en la piel periestomal, en este caso, nos centramos en los granulomas que supondrán picor, dolor y limitaciones en el autocuidado. Observando la evolución de nuestro caso, consideramos que la administración de L-metionina podría ser un factor beneficioso para mejorar la calidad de vida del paciente urostomizado. Conclusión: El uso de L-metionina en pacientes con orina alcalina puede suponer una mejoría en la calidad de vida del paciente urostomizado.

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BackgroundPrimary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.MethodsThis prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.ResultsAt follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.ConclusionFor PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Kukoamine A alleviates nephrolithiasis by inhibiting endogenous oxalate synthesis via the IL-6/JAK/STAT3/DAO signaling pathway

BackgroundThe recurrent nature and socioeconomic burden of nephrolithiasis demand effective treatments. Delineating the crosstalk between inflammatory processes and the endogenous oxalate metabolism pathway, which underpins nephrolithiasis pathogenesis, is essential for advancing treatment strategies. PurposeWe aim to screen therapeutic Chinese herbal remedies and their bioactive constituents for kidney stone treatment using a fruit fly model, followed by efficacy and mechanism validation in a rodent nephrolithiasis model as well as in vitro human cell culture model. Study design and methodsWe developed a fruit fly model to screen for efficient traditional Chinese medicine herbs and their active compounds for kidney stone treatment. Candidate active compounds from efficient herbs were separated and identified by solid-phase chromatography coupled with LC-MS analysis. Fruit fly genetic tools were employed to manipulate the expression of related genes to explore the therapeutic mechanisms of the Lycii Cortex and kukoamine A (KuA). To confirm the therapeutic effects and mechanisms of KuA for mammalian nephrolithiasis, mouse model of glyoxylate-induced kidney stone and human renal tubular cells were used. The therapeutic role of kukoamine A in nephrolithiasis was evaluated by assessing tubular injury, crystal deposition, and adhesion. The level of expression and phosphorylation in cells and mice was assessed using RT-qPCR and western blot. ResultsOur findings indicate that Lycii Cortex potently inhibits calcium oxalate stone formation via activation of the JNK/Upd3/JAK/STAT signaling cascade, resulting in diminished endogenous oxalate synthesis by downregulating D-amino acid oxidase (DAO) gene expression, predominantly in fruit fly Malpighian tube stellate cells. KuA was identified as the principal bioactive constituent mediating these effects. Both mouse models and human cell assays confirmed KuA's efficacy in preventing calcium oxalate nephrolithiasis in mammals, through hepatic JAK/STAT3 pathway activation and upregulation of IL-6, culminating in reduced urinary crystal deposition. ConclusionOur research underscores the potential of kukoamine A as a lead compound in treating nephrolithiasis and reveals the interplay between the IL-6/JAK/STAT3 inflammatory pathway and endogenous oxalate metabolism in nephrolithiasis pathogenesis. Additionally, it highlights the utility of the fruit fly model as a powerful tool for deciphering the therapeutic mechanisms of traditional Chinese herbs.

Establishment of a Solubility Test for the Differentiation of Urine Crystals

Establishment of a Solubility Test for the Differentiation of Urine Crystals

In Vitro and In Vivo Antiurolithic Effect of Betulinic Acid Obtained from Citharexylum mirianthum.

The study aimed to investigate the potential antiurolithic effects of extracts, fractions, and betulinic acid (BA) from Citharexylum mirianthum. In vitro analysis involved precipitating calcium oxalate (CaOx) crystals in urine. For in vivo studies, rats were divided into four groups: naive; vehicle; potassium citrate (KC); and BA. Urolithiasis was induced using ethylene glycol and ammonium chloride. After seven days, urine, blood, and kidney tissues were evaluated. The results showed that methanolic extract, hexane, dichloromethane, and ethyl acetate fractions, as well as BA, reduced CaOx crystal formation. In vivo, the vehicle-treated group exhibited reduced urinary volume and Na+ excretion, while the BA-treated group showed restored urinary volume and Na+ excretion similar to the naive group. BA also significantly reduced urinary monohydrate and dihydrate crystal formation, comparable to the KC group. Other urinary parameters remained unchanged, but plasma analysis revealed decreased Na+, K+, and Ca2+ in the KC group. Renal tissue analysis indicated reduced lipid hydroperoxides and increased reduced glutathione in all urolithiasis groups, with unchanged nitrite levels. BA treatment also improved renal corpuscle morphology. Overall, our findings demonstrate that treatment with BA effectively prevented kidney damage induced by EG+AC ingestion, thereby improving renal function in the urolithiasis model.

Effect of Some Algerian Saharan Medicinal Plants on Brushite Crystallization in Artificial Urine

Effect of Some Algerian Saharan Medicinal Plants on Brushite Crystallization in Artificial Urine

Spectrophotometric and chromatographic analysis of creatine:creatinine crystals in urine

Creatinine is the end product of the catabolism of creatine and creatine phosphate. Creatine phosphate serves as a reservoir of high-energy phosphate, especially in skeletal and cardiac muscle. Besides typical known changes in serum and urinary creatinine concentrations, rare cases associated with changes in serum and urinary creatine levels have been described in the literature in humans. These cases are mostly linked to an excessive intake of creatine ethyl ester or creatine monohydrate, often resulting in increased urine creatinine concentrations. In addition, it is known that at such elevated creatinine concentrations, creatinine crystallisation may occur in the urine. Analysis of crystals and urinary concrements, often of heterogenous chemical composition, may provide diagnostic and therapeutic hints to the benefit of the patient. The aim of the present work was to analyze urine crystals of unclear composition with microscopic and spectroscopic techniques.On routine microscopic analysis of urine, a preliminary suspicion of uric acid or creatinine crystals was expressed. The crystals were of a cuboid shape and showed polarization effects in microscopy. The dried urine sample was whitish-orange in colour, odourless and dissolved well in water. Protein concentration in dry weight (DW) urine was about 0.3 mg/mg. The measured zinc content in the studied sample was approximately 660 µg/g DW sample and copper content was approximately 64 µg/g DW sample. A lead signal of around 10 µg/g DW sample was also observed. UV–Vis analysis showed a maximum creatine peak around 220 nm, compatible with the spectrum of creatinine with a maximum peak of 230 nm. Using HPLC technique, an extreme high ratio of creatine to creatinine of about 38 was measured, which led to the conclusion of the occurrence of rare creatine crystals in urine.

8-l-Cystinyl Bis(1,8-diazaspiro[4.5]decane) as an Orally Bioavailable l-Cystine Crystallization Inhibitor for Cystinuria.

Cystinuria, a rare genetic disorder, is characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of l-cystine and subsequent l-cystine crystallization in urine and stone formation in the urinary tract. Inhibition of l-cystine crystallization by l-cystine diamides such as LH708 (2) represents a promising new approach to prevent stone formation in patients with cystinuria. While 2 shows promising in vivo efficacy and a good safety profile in a Slc3a1-knockout mouse model of cystinuria, further structural modification of 2 led to the discovery of 8-l-cystinyl bis(1,8-diazaspiro[4.5]decane) (LH1753, 3) incorporating a bioisosteric spiro bicyclic diamine 1,8-diazaspiro[4.5]decane for the N-methylpiperazine terminal groups in 2 as a promising candidate with 3 being about 120× more potent than l-cystine dimethyl ester (CDME, 1) and about 2× more potent than 2 in inhibiting l-cystine crystallization. Furthermore, 3 demonstrated good oral bioavailability and in vivo efficacy in preventing l-cystine stone formation in the Slc3a1-knockout mouse model of cystinuria.

Establishment of an artificial urine model in vitro and rat or pig model in vivo to evaluate urinary crystal adherence

The current study aimed to establish an experimental model in vitro and in vivo of urinary crystal deposition on the surface of ureteral stents, to evaluate the ability to prevent crystal adhesion. Non-treated ureteral stents were placed in artificial urine under various conditions in vitro. In vivo, ethylene glycol and hydroxyproline were administered orally to rats and pigs, and urinary crystals and urinary Ca were investigated by Inductively Coupled Plasma-Optical Emission Spectrometer. in vitro, during the 3- and 4-week immersion periods, more crystals adhered to the ureteral stent in artificial urine model 1 than the other artificial urine models (p < 0.01). Comparing the presence or absence of urea in the composition of the artificial urine, the artificial urine without urea showed less variability in pH change and more crystal adhesion (p < 0.05). Starting the experiment at pH 6.3 resulted in the highest amount of crystal adhesion to the ureteral stent (p < 0.05). In vivo, urinary crystals and urinary Ca increased in rat and pig experimental models. This experimental model in vitro and in vivo can be used to evaluate the ability to prevent crystal adhesion and deposition in the development of new ureteral stents to reduce ureteral stent-related side effects in patients.

Enhanced long-term performance of ureteral stents with functional coating: Combating bacterial adhesion and inhibiting encrustation

Long-term indwelling ureteral stents in urology surgeries often lead to severe encrustation and challenging clinical complications, necessitating an effective medical response. Although many researchers have started with antibacterial, anti-fouling and other aspects, the lack of direct urinary pertinence or develop drug resistance have not really improved the current situation of crust. Therefore, while giving full play to the excellent properties of coated anti-bacterial adhesion, it is still a challenging problem to ensure that it can be effectively applied to ureteral stents and urinary tract environment. Herein, this work proposes a practical functional coating to inhibit encrustation, achieved by incorporating the urinary crystal inhibitor citric acid to crosslink the polyvinylpyrrolidone with hydrophilic lubrication properties (PVP/CA). The coating based on charge interaction has excellent stability (peel strength up to 600 N/m) excellent wettability (contact angle reduced by 60°), lubricity (friction coefficient reduced by 4 times) and biocompatibility. More importantly, the synergistic anti-bacteria adhesion (>90 %) and inhibition of urinary tract crystallization properties of the coated ureteral stent demonstrate superior performance in preventing encrustation over a 4-week period in an in vitro model. This innovative coating strategy holds promising prospects for ureteral stents, offering a potential solution to alleviate pain in urological patients.

Structure-activity relationships and pharmacokinetic evaluation of L-cystine diamides as L-cystine crystallization inhibitors for cystinuria

Cystinuria is a rare genetic disorder characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of L-cystine and subsequent l-cystine crystallization and stone formation in urine. l-Cystine diamides have shown great promise as inhibitors of l-cystine crystallization. The free α-amino groups in l-cystine diamides have previously been shown to be necessary for l-cystine crystallization inhibitory activity. In this study, three additional series of l-cystine diamide analogs were designed to explore further the structure-activity relationships for l-cystine crystallization inhibition. It has been demonstrated that the middle disulfide bond is required for optimal l-cystine crystallization inhibitory activity, and the only regions that can be modified are the two terminal amides. The presence of another basic amine 2–3 atoms away from the amide nitrogen is also critical for optimal activity. Disulfide exchange was found to be the main metabolic pathway resulting in the formation of two molecules of the active mixed disulfide metabolite from a single l-cystine diamide. l-Cystine diamides have the potential to be developed into a much-needed therapy for cystinuria.

Correlation analysis between urinary crystals and upper urinary calculi

ObjectiveTo analyze the correlation between urinary crystals and urinary calculi. MethodsClinical data, including urinary crystal types, were collected from 237 patients with urinary calculi. The detection rate of urine crystals and their correlation with stone composition were analyzed. Receiver operating characteristic curve analysis was used to determine the best cut-off value for predicting stone formation risk based on calcium oxalate crystals in urine. ResultsCalcium oxalate was the most common component in 237 patients. Among them, 201 (84.81%) patients had stones containing calcium oxalate. In these patients, calcium oxalate crystals were detected in 45.77% (92/201) of cases. In different groups of calcium oxalate stones, calcium oxalate crystals accounted for more than 90% of the total number of crystals detected in each group. The detection rate of calcium oxalate crystals was higher in first-time stone formers and those with kidney stones. The receiver operating characteristic curve analysis suggested a cut-off value of 110 crystals/μL for predicting stone formation, validated with 65 patients and 100 normal people. ConclusionCalcium oxalate crystals in urine can predict the composition of calcium oxalate stones and indicate a higher risk of stone formation when their number exceeds 110 crystals/μL. This non-invasive method may guide clinical treatment and prevention strategies.

Analysis of creatinine crystals in urine by spectrophotometric and chromatographic methods

Analysis of creatinine crystals in urine by spectrophotometric and chromatographic methods

Artificial intelligence to improve urine crystals recognition

Artificial intelligence to improve urine crystals recognition

Examination of Calcium Oxalate Crystals In Mountain Water Consumers In Kuningan Regency

Urine, a byproduct of metabolism occurring in the kidneys, serves as a crucial diagnostic medium in laboratory settings, including the microscopic examination of calcium oxalate crystals. Influenced by various factors, such as demographics and environmental conditions, the formation of these crystals underscores broader health considerations. Mountain water, renowned for its mineral content, constitutes a significant source of daily hydration. However, the dominance of calcium and magnesium elements in surface water raises concerns regarding calcium oxalate crystallization. This study investigates the prevalence of calcium oxalate crystals in mountain water consumers within Kuningan Regency. Employing descriptive research methods and random sampling techniques, the study examined urine samples from 38 individuals. Results revealed calcium oxalate crystals in 11 participants, constituting 28.95% of the sample. This finding underscores the need for further research into water quality and its implications for public health in the region. By elucidating the relationship between water composition and urinary crystal formation, this study informs strategies for safeguarding community health and informs future policy initiatives regarding water resource management.

Targeting urinary calcium oxalate crystallization with inulin-type AOFOS from Aspidopterys obcordata Hemsl. for the management of rat urolithiasis

Ethnopharmacological relevance:Calcium oxalate crystals play a key role in the development and recurrence of kidney stones (also known as urolithiasis); thus, inhibiting the formation of these crystals is a central focus of urolithiasis prevention and treatment. Previously, we reported the noteworthy in vitro inhibitory effects of Aspidopterys obcordata fructo oligosaccharide (AOFOS), an active polysaccharide of the traditional Dai medicine Aspidopterys obcordata Hemsl. (commonly known as Hei Gai Guan), on the growth of calcium oxalate crystals. Aim of the study:To investigated the effectiveness and mechanism of AOFOS in treating kidney stones. Materials and methods:A kidney stones rats model was developed, followed by examining AOFOS transport dynamics and effectiveness in live rats. Additionally, a correlation between the polysaccharide and calcium oxalate crystals was studied by combining crystallization experiments with density functional theory calculations. Results:The results showed that the polysaccharide was transported to the urinary system. Furthermore, their accumulation was inhibited by controlling their crystallization and modulating calcium ion and oxalate properties in the urine. Consequently, this approach helped effectively prevent kidney stone formation in the rats. Conclusions:The present study emphasized the role of the polysaccharide AOFOS in modulating crystal properties and controlling crystal growth, providing valuable insights into their potential therapeutic use in managing kidney stone formation.

PERSIAN CAT WITH STAPHYLOCOCCUS SP. CYSTITIS

The vesica urinaria is inflamed in cystitis. The pH of the urine, the amount of food consumed, and bacterial infection are all factors that can contribute to infection and the production of uroliths. This article seeks to learn more about the procedures for diagnosing, managing, and treating feline cystitis problems. A male, black Persian cat with a body weight of 4.9 kg, two years old. With complaints of hematuria throughout the previous two days and complains of incontinence and inability to urinate with much volume. Urinary vesica wall thickening was discovered during ultrasound examination, along with urinary vesica crystals. Urinalysis, hematology testing, and urine culture were done. As a crystal breaker in the urinary vesica, ciprofloxacin dexamethasone and Batugin herbal medication were administered to the case animal. Change the cat diet and feed used for urinary care. One week after starting the therapy, the cat appeared in good health, peeing normally and without any signs of pain or blood. Based on macroscopic examination, the cat's urine was yellow and free of blood. The cat's urine was examined under a microscope, and no crystals were found. After seven days of medication, the case cat had positive effects. Smooth urination started, and there was no sign of stranguria, oliguria, or hematuria.

Sulfamethoxazole-induced crystal nephropathy: characterization and prognosis in a case series

Cotrimoxazole (Trimethoprim/Sulfamethoxazole-SMX) is frequently used in critically ill and immunocompromised patients. SMX is converted to N-acetyl-sulfamethoxazole (NASM) and excreted by the kidneys. NASM may form crystals in urine, especially in acid urine, that may induce a crystalline nephropathy. However, the imputability of crystals in acute kidney injury (AKI) has not been proven. We aimed to assess whether NASM crystals may promote AKI and to investigate risk factors associated with NASM crystalline nephropathy. Patients from Ile-de-France, France who developed AKI under SMX treatment introduced during hospitalization and had a crystalluria positive for NASM crystals were selected. Patients with excessive preanalytical delay for crystalluria or missing data regarding SMX treatment were excluded. We used the Naranjo score to assess the causal relationship between SMX and the development of AKI in patients with positive NASM crystalluria. Fourteen patients were included. SMX was the probable cause of AKI for 11 patients and a possible cause for 3 patients according to Naranjo score. Patients were exposed to high doses of SMX (but within recommended ranges), and most of them had a preexisting chronic kidney disease and were hypoalbuminemic. Urine pH was mildly acid (median 5.9). AKI occured more rapidly than expected after introduction of SMX (median 4 days) and recovered rapidly after drug discontinuation in most, but not all, cases. SMX is a probable cause of crystalline nephropathy. Monitoring of crystalluria in patients exposed to SMX may be of interest to prevent the development of crystalline nephropathy. Approval number of the study: BPD-2018-DIAG-008.

Sex-specific Stone-forming Phenotype in Mice During Hypercalciuria/Urine Alkalinization

Sex differences in kidney stone formation are well known. Females generally have slightly acidic blood and higher urine pH when compared with males, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide and calcium gluconate supplementation, respectively, for 4 weeks in wild-type (WT) and moderately hypercalciuric [TRPC3 knockout [KO](−/−)] male and female mice. Our goal was to develop calcium phosphate (CaP) and CaP+ calcium oxalate mixed stones in our animal model to understand the underlying sex-based mechanism of calcium nephrolithiasis. Our results from the analyses of mice urine, serum, and kidney tissues show that female mice (WT and KO) produce more urinary CaP crystals, higher [Ca2+], and pH in urine compared to their male counterparts. We identified a sex-based relationship of stone-forming phenotypes (types of stones) in our mice model following urine alkalization/calcium supplementation, and our findings suggest that female mice are more susceptible to CaP stones under those conditions. Calcification and fibrotic and inflammatory markers were elevated in treated female mice compared with their male counterparts, and more so in TRPC3 KO mice compared with their WT counterparts. Together these findings contribute to a mechanistic understanding of sex-influenced CaP and mixed stone formation that can be used as a basis for determining the factors in sex-related clinical studies.

Inhibitory Potential of Tribulus terrestris on Calcium Oxalate Crystals, Struvite Crystals and Bacterial Pathogens: A Preliminary Investigation

Kidney stone formation and recurring urinary tract infection (UTIs) are common among the general population. An alternative herbal treatment potential was investigated in this study. This study aims to investigate anti-urolithiasis efficacy of herbal Tribulus terrestris (TT) plant leaf extract in reducing the growth of calcium oxalate and struvite crystal using in vitro methods. In vitro antiurolithiatic potential of TT leaf extract was studied using nucleation, aggregation, and crystal formation assays in synthetic media and in synthetic urine samples. In vitro antiurolithiasis potential of Tribulus terrestris (TT) plant leaf extract was investigated at concentrations ranging from 100 to 1000 μg/ml. Initially, the principal phytochemical constituents of TT methanolic leaf extract was examined. Then antibacterial properties of TT plant leaf extract were tested against common urinary tract pathogens such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results of the nucleation assay revealed that TT leaf extract reduced up to 55% of calcium oxalate (CaOx) crystallization and inhibits struvite crystal formation up to 85% with 5% (0.43 g) of TT extract. This study revealed a dose-dependent suppression of crystal formation by increased TT plant leaf extract dosage. The antibacterial activity of TT plant leaf extract is greater against E. coli than S. aureus. This anti-urolithiasis potential of TT plant extract can be used as an antidote for individuals who are prone to urinary crystal formation as well as to control urinary tract infections.