Baicalin attenuated oxidative stress and inflammation in ethylene glycol-induced urolithiasis in adult male SD rats.

AIMS: Baicalin is a flavonoid derived from the root of the medicinal plant Scutellaria baicalensis Georgi (S. baicalensis) and is known for its various pharmacological properties. This study aimed to investigate the impact of baicalin (BAI) on the occurrence of kidney calcium oxalate crystal formation induced by ethylene glycol in male SD rats. MAIN METHODS: A rat model of renal stones was created and various concentrations of baicalin were used for intervention. Samples of urine, blood, and kidney tissue were taken from the rats, and they were euthanized for biochemical and histopathological examinations. KEY FINDINGS: Our results show that baicalin treatment improved the weight loss induced by ethylene glycol (EG) and ammonium chloride (AC) in rats. Baicalin also reduced the formation of calcium oxalate crystals and protected kidney function in rats with urolithiasis. Furthermore, it lowered the level of malondialdehyde (MDA) and elevated the activity of antioxidant enzymes compared to the stone control group. Additionally, baicalin notably alleviated renal inflammation in rats with urolithiasis. SIGNIFICANCE: The present study attributed clinical evidence first time that claiming the significant antiurolithic effect of baicalin and could be a cost-effective candidate for the prevention and treatment of urolithiasis.

Cell death­related molecules and targets in the progression of urolithiasis (Review).

Urolithiasis is a high­incidence disease caused by calcium oxalate (mainly), uric acid, calcium phosphate, struvite, apatite, cystine and other stones. The development of kidney stones is closely related to renal tubule cell damage and crystal adhesion and aggregation. Cell death, comprising the core steps of cell damage, can be classified into various types (i.e., apoptosis, ferroptosis, necroptosis and pyroptosis). Different crystal types, concentrations, morphologies and sizes cause tubular cell damage via the regulation of different forms of cell death. Oxidative stress caused by high oxalate or crystal concentrations is considered to be a precursor to a variety of types of cell death. In addition, complex crosstalk exists among numerous signaling pathways and their key molecules in various types of cell death. Urolithiasis is considered a metabolic disorder, and tricarboxylic acid cycle­related molecules, such as citrate and succinate, are closely related to cell death and the inhibition of stone development. However, a literature review of the associations between kidney stone development, metabolism and various types of cell death is currently lacking, at least to the best of our knowledge. Thus, the present review summarizes the major advances in the understanding of regulated cell death and urolithiasis progression.

In vivo investigation of the inhibitory effect of Peganum harmala L. and its major alkaloids on ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.

Clinicopathologic findings and urolith composition for green iguanas (Iguana iguana) with urolithiasis: 21 cases and 132 stones (1996-2020).

OBJECTIVE: To document the clinical signs, diagnosis, and treatment of urolithiasis in green iguanas (Iguana iguana) and to report on the composition of uroliths from green iguanas submitted to the Minnesota Urolith Center for analysis. ANIMALS: 21 green iguanas with urolithiasis. PROCEDURES: Medical record databases of multiple veterinary teaching hospitals were searched from 1996 through 2020. Emails were sent to all facilities that submitted a urolith from a green iguana to the Minnesota Urolith Center from 1996 through 2020. Signalment; presenting complaint; physical examination findings; hematologic, biochemical, and diagnostic imaging findings; treatment; necropsy results; and survival times were described for each patient. RESULTS: Iguanas most commonly presented with nonspecific clinical signs, but 9 of the 21 iguanas had clinical signs associated with the urogenital tract. Twelve iguanas had a palpable mass in the caudal coelom. All uroliths were visible on radiographs. Surgery was performed on 15 iguanas; 3 died secondary to intra- or postoperative complications. Iguanas that underwent surgery had a median survival time of 39 months. Necropsy was performed on 5 iguanas, and urolithiasis contributed to the decision to euthanize or was the cause of death for 4. Uroliths from 132 iguanas were analyzed, and all were composed of 100% uric acid salts. CLINICAL RELEVANCE: Green iguanas with urolithiasis may not have clinical signs or physical examination findings associated with the urinary system, and hematologic and biochemical abnormalities are nonspecific. Green iguanas should be routinely examined for uroliths, and surgical treatment should be pursued.

Protective effect of apigenin on ethylene glycol-induced urolithiasis via attenuating oxidative stress and inflammatory parameters in adult male Wistar rats.

AIMS: Apigenin (4',5,7-trihydroxyflavone) is one of the subclasses of flavonoids and has various pharmacological effects. The present work was carried out to study the effect of apigenin on ethylene glycol-induced kidney damage in male Wistar rats. MAIN METHODS: We evaluated the effects of apigenin orally administrated in normal and urolithiatic rats. Animals were assigned to nine groups in random: normal control; apigenin alone (0.005, 0.01, and 0.02 g/kg bw); urolithiatic control (0.75% ethylene glycol and 1.0% ammonium chloride in drinking water); apigenin (0.005, 0.01, and 0.02 g/kg bw) plus ethylene glycol and ammonium chloride; and cystone (0.75 g/kg bw) plus ethylene glycol and ammonium chloride. At the end of 28th day of treatment, animals were sacrificed for biochemical and histopathological assays. KEY FINDINGS: Our results indicated that the apigenin treatment decreased the formation of urinary stones in urolithiatic rats. Also, apigenin reduced the generation of malondialdehyde and enhanced antioxidant enzymes activities in the kidney homogenate of rats. It also caused a significant decrease in the calcium oxalate crystals numbers in urinary sample of rats with ethylene glycol-induced hyperoxaluria. These findings were supported by histopathological examinations. SIGNIFICANCE: Based on the results obtained, apigenin attenuate ethylene glycol-related kidney damage in male Wistar rats. Although the underlying mechanism of apigenin effect has not been determined, reduction of urinary levels of stone-producing constituents, antioxidant activities, and inhibition of TGF-ß signaling may be involved.

Nephroprotective Effect of Pleurotus ostreatus and Agaricus bisporus Extracts and Carvedilol on Ethylene Glycol-Induced Urolithiasis: Roles of NF-κB, p53, Bcl-2, Bax and Bak.

This study was designed to assess the nephroprotective effects of Pleurotus ostreatus and Agaricus bisporus aqueous extracts and carvedilol on hyperoxaluria-induced urolithiasis and to scrutinize the possible roles of NF-κB, p53, Bcl-2, Bax and Bak. Phytochemical screening and GC-MS analysis of mushrooms' aqueous extracts were also performed and revealed the presence of multiple antioxidant and anti-inflammatory components. Hyperoxaluria was induced in Wistar rats through the addition of 0.75% (v/v) ethylene glycol in drinking water for nine weeks. The ethylene glycol-administered rats were orally treated with Pleurotus ostreatus and Agaricus bisporus aqueous extracts (100 mg/kg) and carvedilol (30 mg/kg) daily during the last seven weeks. The study showed that Pleurotus ostreatus, Agaricus bisporus and carvedilol all successfully inhibited ethylene glycol-induced histological perturbations and the elevation of serum creatinine, serum urea, serum and urinary uric acid, serum, urinary and kidney oxalate, urine specific gravity, kidney calcium, kidney NF-κB, NF-κB p65, NF-κB p50, p53, Bax and Bak expressions as well as serum TNF-α and IL-1ß levels. Moreover, the treatment decreased the reduction in urinary creatinine, urinary urea, ratios of urinary creatinine to serum creatinine and urinary urea to serum urea, Fex Urea and Bcl-2 expression in kidney. In conclusion, although Pleurotus ostreatus and Agaricus bisporus extracts and carvedilol all significantly inhibited the progression of nephrolithiasis and showed nephroprotective effects against ethylene glycol-induced kidney dysfunction, Pleurotus ostreatus and Agaricus bisporus seemed to be more effective than carvedilol. Moreover, the nephroprotective effects may be mediated via affecting NF-κB activation, extrinsic apoptosis and intrinsic apoptosis pathways.

iTRAQ-Based Comparative Proteomics Analysis of Urolithiasis Rats Induced by Ethylene Glycol.

Nephrolithiasis is a frequent chronic urological condition with a high prevalence and recurrence rate. Proteomics studies on urolithiasis rat models are highly important in characterizing the pathophysiology of kidney stones and identifying potential approaches for preventing and treating kidney stones. The isobaric tags for relative and absolute quantification (iTRAQ) were performed to identify differentially expressed proteins (DEPs) in the kidney between urolithiasis rats and control rats. The results showed that 127 DEPs (85 upregulated and 42 downregulated) were identified in urolithiasis and control rats. The functions of DEPs were predicted by Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis. The expression of four upregulated proteins (Tagln, Akr1c9, Spp1, and Fbn1) and four downregulated proteins (Hbb, Epb42, Hmgcs2, and Ca1) were validated by parallel reaction monitoring (PRM). Proteomics studies of ethylene glycol-induced urolithiasis rat models using iTRAQ and PRM helped to elucidate the molecular mechanism governing nephrolithiasis and to identify candidate proteins for the treatment of kidney stones.

[Crystalline pathologies in the human body: first steps of pathogenesis]. / Les pathologies cristallines humaines : les premières étapes de la pathogénèse.

The prevalence of crystalline pathologies including urolithiasis, gallstones, vascular calcifications and crystalline arthritis, is very high in the general population beyond 60 years old. Characterization of microcrystals in tissue at the micrometer and at the nanometer scale through physico-chemical techniques constitutes a new opportunity for the physician to decipher the early stage of the pathogenesis of these biological entities. In this review, such description indicates a wide variety of the chemical process associated to the nucleation process directly from supersaturated solution or from organic support such as DNA or elastin. We will also discuss the case of vesicles which play a major role in the case of ectopic calcification situated in kidney tissue, namely the Randall's plaque. All this research focused on the very first steps of the genesis of pathological calcifications constitute a major step to develop specific therapy able to avoid the formation of these abnormal deposits in tissues. As already underlined, crystals may be the consequence of various pathologies, but they are also involved in the dysfunction of the tissues.

Cellular and Molecular Mechanisms of Kidney Injury in 2,8-Dihydroxyadenine Nephropathy.

BACKGROUND: Hereditary deficiency of adenine phosphoribosyltransferase causes 2,8-dihydroxyadenine (2,8-DHA) nephropathy, a rare condition characterized by formation of 2,8-DHA crystals within renal tubules. Clinical relevance of rodent models of 2,8-DHA crystal nephropathy induced by excessive adenine intake is unknown. METHODS: Using animal models and patient kidney biopsies, we assessed the pathogenic sequelae of 2,8-DHA crystal-induced kidney damage. We also used knockout mice to investigate the role of TNF receptors 1 and 2 (TNFR1 and TNFR2), CD44, or alpha2-HS glycoprotein (AHSG), all of which are involved in the pathogenesis of other types of crystal-induced nephropathies. RESULTS: Adenine-enriched diet in mice induced 2,8-DHA nephropathy, leading to progressive kidney disease, characterized by crystal deposits, tubular injury, inflammation, and fibrosis. Kidney injury depended on crystal size. The smallest crystals were endocytosed by tubular epithelial cells. Crystals of variable size were excreted in urine. Large crystals obstructed whole tubules. Medium-sized crystals induced a particular reparative process that we term extratubulation. In this process, tubular cells, in coordination with macrophages, overgrew and translocated crystals into the interstitium, restoring the tubular luminal patency; this was followed by degradation of interstitial crystals by granulomatous inflammation. Patients with adenine phosphoribosyltransferase deficiency showed similar histopathological findings regarding crystal morphology, crystal clearance, and renal injury. In mice, deletion of Tnfr1 significantly reduced tubular CD44 and annexin two expression, as well as inflammation, thereby ameliorating the disease course. In contrast, genetic deletion of Tnfr2, Cd44, or Ahsg had no effect on the manifestations of 2,8-DHA nephropathy. CONCLUSIONS: Rodent models of the cellular and molecular mechanisms of 2,8-DHA nephropathy and crystal clearance have clinical relevance and offer insight into potential future targets for therapeutic interventions.

Antiurolithiatic activity of Boldoa purpurascens aqueous extract: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Boldoa purpurascens Cav. (Nyctaginaceae) is a plant species used in traditional medicine in Cuba as antiurolithiatic. AIM OF THE STUDY: The aim of the present investigation was to evaluate the in vitro and in vivo antiurolothiatic activity of an aqueous extract from the leaves of Boldoa purpurascens. MATERIALS AND METHODS: The aqueous extract from leaves of Boldoa purpurascens was evaluated for antiurolithiatic activity in vitro and in vivo. In vitro crystallization of calcium oxalate (CaOx) was assessed using a nucleation, aggregation and growth assay. The effects of the extract and of Cystone®, used as a positive control, on the slope of nucleation and aggregation, as well as on the growth of CaOx crystals, were evaluated spectrophotometrically. The densities of the formed crystals were compared microscopically. In vivo activity was evaluated in an urolithiasis model in rats, in which kidney stones are induced by ethylene glycol (0.75%) and ammonium chloride (2%) in drinking water for 10 days. Three different experimental doses (100, 200 and 400 mg/kg, p.o.) of the extract and Cystone® were administered for 10 days. After 10 days, various biochemical parameters were measured in urine and serum, and histopathological analysis of the kidneys was carried out. RESULTS: The aqueous extract of Boldoa purpurascens inhibited the slope of nucleation and aggregation of CaOx crystallization, and decreased the crystal density. It also inhibited the growth and caused the dissolution of CaOx crystals. Cystone® exhibited similar effects. At a dose of 400 mg/kg the extract reduced the concentration of uric acid in urine, as well as the serum concentration of uric acid and creatinine. Histopathologic analysis of the kidneys of the same treatment group revealed reduced tissue damage; the results were almost similar to the untreated healthy control group. CONCLUSION: This study indicates that an aqueous leaf extract of Boldoa purpurascens may be effective in the prevention of urinary stone formation, and substantiates the traditional claim.

Rare crystalline nephropathy leading to acute graft dysfunction: a case report.

BACKGROUND: Adenine phosphoribosyl transferase (APRT) deficiency is a rare genetic form of kidney stones and/or kidney failure characterized by intratubular precipitation of 2,8 dihydroxyadenine crystals. Early diagnosis and prompt management can completely reverse the kidney injury. CASE PRESENTATION: 44 year old Indian male, renal transplant recipient got admitted with acute graft dysfunction. Graft biopsy showed light brown refractile intratubular crystals with surrounding giant cell reaction, consistent with APRT deficiency. Patient improved after receiving allopurinol and hydration. CONCLUSION: APRT forms a reversible cause of crystalline nephropathy. High index of suspicion is required for the correct diagnosis as timely diagnosis has therapeutic implications.

The role of selected environmental factors and the type of work performed on the development of urolithiasis - a review paper.

Urolithiasis is a disease of the genitourinary system, which is defined as the presence of urinary stones at any place in the urinary tract, resulting from the precipitation reaction of chemical compounds. The aim of this study is to demonstrate the important role of selected environmental factors (climate, ambient temperature) and the type of profession performed in the development of urolithiasis. In this field, the literature including original and review papers related to the epidemiology, pathogenesis and risk factors of urolithiasis was analyzed. The study used electronic databases such as Medline, Web of Science and Google Scholar. The prevalence of urolithiasis has increased in recent decades in both developed and developing countries. It is believed that this growing trend is associated with lifestyle changes such as the lack of physical activity, poor eating habits and global warming. Many factors are responsible for the formation of urinary stones. In literature, there is a division into individual and environmental factors. Today, external factors in the form of climate changes (global warming), geographical conditions and seasonal fluctuations, and the type of profession performed are becoming more and more important in the context of the occurrence of urinary stones. Currently, the presence of urolithiasis is becoming a significant problem all over the world and searching for causes is not easy, but particular attention should be paid to certain predispositions resulting from environmental factors, such as ambient temperature and the type of work performed. Int J Occup Med Environ Health. 2019;32(6):761-75.

Pioglitazone decreased renal calcium oxalate crystal formation by suppressing M1 macrophage polarization via the PPAR-γ-miR-23 axis.

Interaction of pioglitazone (PGZ) and macrophages (Mps) in renal crystal formation remains unclear. In the present study, we investigated the possible mechanisms involved with Mps of PGZ in suppressing renal crystal formation. Crystal formation in the mouse kidney was detected using polarized light optical microscopy and Pizzolato staining. Gene expression was detected by Western blot analysis, quantitative RT-PCR, immunohistochemistry, immunofluorescence, and ELISA. Mp phenotypes were identified by flow cytometric analysis. Cell apoptosis was detected with TUNEL assay, and tubular injury was detected with periodic acid-Schiff staining. Interaction of peroxisome proliferator-activated receptor (PPAR)-γ and promoter was determined by chromatin immunoprecipitation assay. Luciferase reporter assay was performed to authenticate target genes of miRNA-23 (miR-23). Recombinant adenovirus was used to elucidate the role of miR-23 in vivo. Renal crystal formation, inflammation, tubular injury, and cell apoptosis were significantly marked in glyoxylic acid-treated groups and significantly decreased in PGZ-treated groups. PGZ significantly reduced Mp infiltration and M1 Mp polarization in the kidney. In vitro, PGZ shifted crystal-stimulated M1-predominant Mps to M2-predominant Mps, which were anti-inflammatory. PPAR-γ could directly bind to one PPAR-γ regulatory element in the promoter of pre-miR-23 to promote expression of miR-23 in Mps. We identified two downstream target genes of miR-23, interferon regulatory factor 1 and Pknox1. Moreover, miR-23 decreased crystal deposition, M1 Mp polarization, and injury in the kidney. This study has proven that PGZ decreased renal calcium oxalate crystal formation and renal inflammatory injury by suppressing M1 Mp polarization through a PPAR-γ-miR-23-interferon regulatory factor 1/Pknox1 axis. PGZ is liable to be a potential therapeutic medicine for treating urolithiasis.

Local Anesthetic Flexible Ureterorenoscopy in the Management of Urolithiasis.

Introduction: Patients unfit for general anesthesia who present with renal tract pathology currently have limited options. Many of these patients present in the emergency setting with imperative reasons for intervention, including sepsis, renal failure, and pain. Conservative management and temporizing measures, such as percutaneous nephrostomy, are associated with significant morbidity. Ureterorenoscopy (URS) is a central component of the management of upper tract disease and is routinely performed under general anesthesia. We describe our institution's experience of URS using only local anesthetic (LA) lubricating gel per urethra. Methods: A single centre, retrospective analysis of 78 patients was performed for an 11 year period. Demographic data and Charlson comorbidity index scoring were collected for all patients. Outcomes, including stone-free rates, tolerability, and complications, were analyzed. Results: In total 58% of patients were men. Mean age was 68 and Charlson comorbidity index was 5.2. Indications for URS included pain (68%) and renal failure (15%). Totally 10% of patients previously had retrograde stenting because of sepsis. Median stone size was 8 mm. All patients were able to tolerate the procedure and none were abandoned because of pain. The overall stone-free rate was 82% after one procedure. The stone-free rate for mid and distal ureteral stones was 97%. Nineteen percent of patients were left with a ureteral stent after the procedure, with the remaining patients left totally tubeless. Median length of stay was 1 day. There were no complications above Clavien Grade 2. Conclusion: Urologists are increasingly faced with unfit patients presenting with urolithiasis. In the appropriately selected patient, LA flexible ureterorenoscopy is a feasible option with good outcomes. This approach is a useful addition to the armamentarium available to patients deemed unsuitable for general or regional anesthesia.

Comparison among the available stone treatment techniques from the first European Association of Urology Section of Urolithiasis (EULIS) Survey: Do we have a Queen?

PURPOSE: The miniaturization of instruments has had an impact on stone management. The aims of this study were to highlight surgeon preferences among Retrograde Intra Renal Surgery (RIRS), Regular, Mini-, UltraMini- and Micro- Percutaneous Nephrolithotomy (PCNL) for urolithiasis and to compare the effectiveness and safety of these techniques in a real-life setting. METHODS: A 12-item survey regarding endourological techniques was conducted through Survey Monkey among attendees of the 2013 European Association of Urology Section of Urolithiasis meeting. We asked responders to share data from the last 5 cases they performed for each technique. Procedures were stratified according to stone size and the centres' surgical volume. Techniques were compared in terms of effectiveness and safety. Analyses were performed on the overall group and a subgroup of 1-2 cm stones. RESULTS: We collected data from a total of 420 procedures by 30, out of 78, urologists who received the survey (response rate 38%): 140 RIRS, 141 Regular-PCNL (>20 Ch), 67 Mini-PCNL (14-20 Ch), 28 UltraMini-PCNL (11-13 Ch) and 44 Micro-PCNL (4,8-8 Ch). Techniques choice was influenced by stone size and the centre's surgical volume. Effectiveness and safety outcomes were influenced by stone size, independently of the technique. The stone-free rate was significantly lower in Micro-PCNL compared to Regular-PCNL. This was not confirmed for 1-2 cm stones. All techniques presented a lower complication rate than Regular-PCNL, with Mini-PCNL being the most protective technique compared to Regular-PCNL. CONCLUSIONS: Stone size seems to drive treatment choice. Miniaturized PCNL techniques are widely employed for 1-2 cm stones, in particular in higher surgical volume centres. Mini-PCNL and RIRS are growing in popularity for stones > 2 cm. Mini-PCNL seems to be a good compromise, being the most effective and safe procedure among PCNL techniques. RIRS is characterized by satisfactory stone-free and low complication rates.

Variables of initial examination and clinical management associated with survival in small ruminants with obstructive urolithiasis.

BACKGROUND: Obstructive urolithiasis is a common disease associated with a guarded prognosis in small ruminants. HYPOTHESIS/OBJECTIVE: The results of physical examination, laboratory analyses, and clinical management of male small ruminants presented to 2 referral clinics were investigated to identify variables significantly associated with disease outcome, so as to provide better recommendations to animal owners regarding the management of these patients. ANIMALS: Two-hundred ten small ruminants (130 sheep and 80 goats) with confirmed diagnosis of obstructive urolithiasis. METHODS: Clinical findings (including diagnostic imaging) and laboratory results of the 210 animals were reviewed, and relevant information regarding clinical and laboratory variables recorded upon admission and clinical management was retrieved. The association of the different variables with nonsurvival was investigated by univariable and multivariable logistic regression models. RESULTS: Only 39% of all patients considered for treatment and 52% of those undergoing tube cystostomy survived to be released from the clinic. Nonsurvival was strongly associated with a very poor clinical condition upon presentation, obesity, castration, and evidence of uroperitoneum. Among blood variables, abnormal PCV, severely increased serum creatinine concentrations, and increased activity of the creatine kinase were associated with increased risk of nonsurvival. Presence of signs of colic or macroscopic appearance of urine was not significantly associated with outcome. CONCLUSIONS AND CLINICAL IMPORTANCE: The prognosis of obstructive urolithiasis was guarded with survival rates of 39% (overall) to 52% (after tube cystostomy). Intact young males with normal body condition presented early in the course of disease had the best chances of survival.

Staphylococcus xylosus Cystitis and Struvite Urolithiasis in Nude Mice Implanted with Sustained-release Estrogen Pellets.

Female nude mice (J:NU-Foxn1nu; age, 6 wk) were injected with 1 million MCF7 human breast cancer cells in the fourth mammary fat pads and received a 21-d sustained-release estrogen pellet (0.25 mg) subcutaneously in the dorsum of the neck. All mice were maintained in sterile housing and provided sterile water and irradiated rodent chow. Approximately 6 wk after implantation, 4 of the 30 mice showed clinical signs of depression and dehydration. The 2 animals most severely affected were euthanized and presented for necropsy. The urinary bladders of these animals were distended with variable sized white, opaque uroliths. Urinalysis revealed coccal bacteria, erythrocytes, neutrophils and struvite crystals. Urine cultures from both necropsied animals grew heavy, pure growths of Staphylococcus xylosus. The organism was sensitive to all antibiotics tested except erythromycin (intermediate). Analysis of the uroliths revealed 100% struvite composition. Remaining mice in the study were evaluated clinically for hydration status, the ability to urinate, and the presence of palpable stones in the urinary bladder; one additional mouse had a firm, nonpainful bladder (urolithiasis suspected). Given the sensitivity of the organisms cultured from urine samples, the remaining mice were placed on enrofloxacin in the drinking water (0.5 mg/mL). All remaining mice completed the study without further morbidity or mortality. Previous studies have reported the association of estrogen supplementation with urinary bladder pathology, including infection and urolithiasis. Here we present a case of urolithiasis and cystitis in nude mice receiving estrogen supplementation that was associated with Staphylococcus xylosus, which previously was unreported in this context. When assessing these nude mice for urolithiasis, we found that visualizing the stones through the body wall, bladder palpation, and bladder expression were helpful in identifying affected mice.

Exposure to imipenem/cilastatin causes nephrotoxicity and even urolithiasis in Wistar rats.

Imipenem/cilastatin is a broad-spectrum ß-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0.9% solution. Nephrotoxic effect of this antibiotic was assessed based on urine and plasma biochemistry, oxidative stress parameters, histopathological examination and infrared spectroscopy characterization. Imipenem/cilastatin administration resulted in alkaline urine, polyuria, crystalluria, raised plasma levels of urea, creatinine and uric acid, decreased contents of plasma gamma glutamyltranspeptidase and alkaline phosphatase, oxidative stress status, malpighian metaplasia as well as crystal deposition in kidneys and urinary tracts of Wistar rats. In addition, the precise nature of the calculi was identified, being formed by imipenem/cilastatin, thus confirming their iatrogenic origin. In conclusion, this study demonstrated through rat model that subacute exposure to imipenem/cilastatin may induce nephrotoxicity and increase the risk for developing kidney stones even at therapeutic dose levels in a dose-dependent manner.

Struvite urolithiasis with eosinophilic polypoid cystitis in a shih tzu dog.

A 7-year-old female spayed shih tzu dog was presented with hematuria of 4 weeks' duration. Radiographs revealed 1 cystic calculus. A polypoid mass was found incidentally during cystotomy and was removed by partial cystectomy. Histopathology revealed eosinophilic polypoid cystitis and urolith analysis reported struvite. A urinary tract infection was treated.

Urolithiase de struvite avec cystite polypoïde éosinophilique chez une chienne Shih tzu. Une chienne Shih Tzu stérilisée âgée de 7 ans a été présentée avec une hématurie d'une durée de 4 semaines. Les radiographies ont révélé un calcul cystique. Une masse poylpoïde a été trouvée accessoirement et enlevée par cystectomie partielle. L'histopathologie a révélé une cystite polypoïde éosiniphilique et l'analyse des urolithes a signalé une struvite. Une infection urinaire a été traitée.(Traduit par Isabelle Vallières).