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.

Role of ferroptosis induced by a high concentration of calcium oxalate in the formation and development of urolithiasis.

Ferroptosis is an iron­dependent lipid peroxidation process. Although the involvement of ferroptosis in kidney diseases has recently been reported, the association between ferroptosis and urolithiasis remains unclear. The present study examined the effects of ferroptosis on calcium oxalate (CaOx) crystal­induced renal tubular epithelial cell injury in vivo and in vitro. First, renal tubular epithelial cells were exposed to various concentrations of CaOx. By measuring cell viability, Fe2+ levels, lipid peroxidation levels and the levels of ferroptosis­related proteins, it was identified that the relative expression of the ferroptosis agonist proteins, p53, long­chain acyl­CoA synthetases (ACSL4), transferrin (TF) and transferrin receptor (TRC), increased, while the relative expression of the ferroptosis inhibitory proteins, solute carrier family 7 member 11 (SLC7A11, XCT) and glutathione peroxidase 4 (GPX4), decreased significantly. Furthermore, the levels of Fe2+ and lipid peroxidation gradually increased, while cell viability significantly decreased. From these results, it was noted that the extent of CaOx­induced ferroptosis activation and cell injury was dependent on the CaOx concentration. To further investigate the association between ferroptosis and renal tubular epithelial cell injury, the ferroptosis agonist, erastin, and the ferroptosis inhibitor, ferrostatin­1, were used to regulate the degree of ferroptosis at the same CaOx concentration in in vivo and in vitro experiments. CaOx­induced ferroptosis and damage to renal tubular epithelial cells and renal tissue were investigated. Finally, it was identified that through the regulation of ferroptosis levels, renal tubular epithelial cell injury increased significantly when the ferroptosis level increased, and vice versa. On the whole, the present results indicated that ferroptosis is essential for renal tubular epithelial cell injury induced by CaOx crystals. This finding is highly significant and promotes the further investigation of the association between ferroptosis and urolithiasis.

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.

Oxidative stress and endoplasmic stress in calcium oxalate stone disease: the chicken or the egg?

Crystal modulators play a significant role in the formation of calcium oxalate stone disease. When renal cells are subjected to oxalate stress, the loss in cell integrity leads to exposure of multiple proteins that assist and/or inhibit crystal attachment and retention. Contact between oxalate and calcium oxalate with urothelium proves fatal to cells as a result of reactive oxygen species generation and onset of oxidative stress. Hence, as a therapeutic strategy it was hypothesised that supplementation of antioxidants would suffice. On the contrary to popular belief, the detection of oxalate induced endoplasmic reticulum mediated apoptosis proved the ineffectiveness of antioxidant therapy alone. Thus, the inadequacy of antioxidant supplementation in oxalate stress invoked the presence of an alternative pathway for the induction of kidney fibrosis in hyperoxaluric rats. In addition to settling this query, the link between oxidative stress and ER stress is not well understood, especially in urolithiasis.

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.

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.

Frailty predicts a higher risk of incident urolithiasis in 525 368 patients with diabetes mellitus: a population-based study.

OBJECTIVE: Patients with diabetes have an increased risk for urolithiasis, but the associated risk factors remain an active area of research. We investigated whether frailty influenced the probability of patients with diabetes developing urolithiasis. RESEARCH DESIGN AND METHODS: Using data from the Longitudinal Cohort of Diabetic Patients from 2004 to 2010, we identified those without and with frailty based on a validated, modified FRAIL scale. Patients were followed until they developed urolithiasis, and we used Kaplan-Meier and Cox proportional hazard regression analyses to examine the relationship between frailty, its severity, and the risk of urolithiasis, accounting for demographic profiles, comorbidities, frailty status changes over follow-up, and medications, with risk competition by mortality. RESULTS: Among 525 368 patients with diabetes, 64.4% were not frail, while 28.5%, 6.6%, and 0.6% had 1, 2, and ≥3 FRAIL items at baseline. After 4.2 years of follow-up, 13.4% experienced incident urolithiasis. Cox proportional hazard regression analysis showed that patients with diabetes having at least one FRAIL criterion exhibited a significantly higher risk for urolithiasis compared with non-frail patients (for 1, 2, and ≥3 items, hazard ratio (HR)s: 1.04, 1.23, and 1.46; 95% confidence intervals (CIs) 0.99 to 1.09, 1.12 to 1.35, and 1.12 to 1.91, respectively). This increase in urolithiasis risk remained significant if we restricted analyses to renal stones or recurrent urolithiasis as the study outcomes. CONCLUSIONS: Frailty may pose a risk for incident urolithiasis in patients with diabetes. Treating frailty may potentially reduce their risk for urolithiasis.

Aggregation of poorly crystalline and amorphous components of infectious urinary stones is mediated by bacterial lipopolysaccharide.

Poorly crystalline and amorphous precipitate (PCaAP) is one of the components of the so-called infectious urinary stones, which are the result of the activity of urease-producing microorganisms, mainly from the Proteus species, in particular Proteus mirabilis. The main component of this kind of stones is crystalline struvite (MgNH4PO4∙6H2O). Bacteria can build into the structure of the urinary stone and, in this way, they are one of the components of the urinary stone. From these three components - PCaAP, struvite and Proteus mirabilis - PCaAP exhibits the greatest ability to aggregate. The present study focuses on the aggregation of PCaAP. In particular, an influence of lipopolysaccharide (LPS) isolated from Proteus mirabilis on aggregation of PCaAP is presented. An aggregation of PCaAP is characterized by cross-sectional area of aggregates and zeta potential. The results demonstrate that, in artificial urine, the influence of freely suspended LPS on aggregation of PCaAP depends on the concentrations of LPS. Small concentrations of freely suspended LPS enhance the aggregation of PCaAP compared to the control test. For high concentrations of freely suspended LPS the formation of aggregates of PCaAP is inhibited. LPS, which is not freely suspended, but covers polystyrene latex beads, has no such properties. The investigations provide evidence for the importance of biological regulation in the PCaAP aggregation process.

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.

Management of urolithiasis in living kidney donors.

BACKGROUND: Kidney donors with asymptomatic stones were  previously excluded from the kidney donation list because of a potential increased morbidity risk for both the recipient and the donor. Currently, recent studies tend to consider these risks as overestimated. AIM: The aim of this study was to analyze our experience in the management of urolithiasis in potential donors. METHODS: We conducted a retrospective analysis during the period (2008-2015). We included donors with urilithiasis or a family history of urolithiasis whom had urinary biochemical analysis of urolithiasis. We identified the exact location, size, and anatomy of the kidney bearing the stone were identified. RESULTS: Among 252 potentially proposed living kidney donors (LKD) in two renal transplantation centers, we noted urinary lithiasis in 8 patients (3.17%). The mean age was 40,12±20 years old with a sex-ratio M/F at 0,3. We noted urinary lithiasis on radiographs in one case, on echographs in one case and on computerized tomography kidney angiography in 5 cases. All are not obese and without any medical history. In one case, there was no lithiasis detected but chemical urinary analysis was performed because of family renal stone history. We performed a 24-hours urine test, and examined PH, calcium and oxalate. The urine analysis, showed acidic pH and hypercalciuria in all cases associated to weddelite in 3 cases, hyperoxaluria in all cases. In one case, we noted vitamin D deficiency related hyperparathyroidism. Renal transplantation has been achieved in two cases. After a mean follow up of 11,25 months [range :27-84], no urological complications were noted. CONCLUSION: Urinary lithiasis may occur in proposed living kidney donors and may not contraindicate this donation.

Prevalence and chemical composition of uroliths in fattening pigs in Belgium.

The present study investigated the prevalence of uroliths in fattening pigs and assessed the composition of these urinary tract concrements. In total, 2,432 urinary bladders were sampled in the slaughterhouse and checked for abnormal content. Urinary samples were analysed microscopically, and samples of the urinary bladder wall were tested for histological signs of inflammation. The composition of the concrements was examined by infrared spectrophotometry. Macroscopic and microscopic abnormalities were detected in 8.4% and 52.8% of the samples respectively. Magnesium ammonium phosphate (struvite), calcium oxalate dihydrate (COD), calcium carbonate (calcite), calcium oxalate monohydrate (COM) and amorphous crystals were detected. Analysis of stones showed COD in all samples in different proportions. The calcium content of examined stones was always considerable (up to 34%), in contrast to the magnesium content which represented max 1.9%. Struvite was found in one third of the samples, but was never part of stones and grit. COD crystals were the second most common microscopic crystal. These COD crystals and some COD stones had a rectangular shape, and therefore, they can be harmful to the bladder mucosa. In conclusion, uroliths are present in a large proportion of male fattening pigs, and consequently, urinary concrements pose a life-threatening risk for urethra obstruction in male pigs. Further research is warranted to identify potential risk factors for urolithiasis and microscopic crystals.

[The features of pathogenesis of urolithiasis in patients with diabetes mellitus type 2].

INTRODUCTION: In recent years, a large number of studies has been published that proved a very significant role of diabetes mellitus type 2 for development of urolithiasis. The aim of our work was to conduct a comparative study of biochemical parameters of blood and urine as well as chemical composition of urinary stones in urolithiasis patients in the general population and in patients with diabetes mellitus type 2. MATERIALS AND METHODS: The work was divided into 2 stages. During the first stage an analysis of chemical composition of urinary stones in the general population (n=5669) and in patients with diabetes mellitus type 2 was carried out (n=350). During the second stage an analysis of biochemical parameters of blood and urine in urolithiasis patients in the general population (n=101) and in patients with diabetes mellitus type 2 was conducted (n=350). RESULTS: In the general population calcium oxalate stones was predominated (56.8%), while phosphate (24.9%) and urate (17.4%) stones were less frequent. In a subgroup of patients with diabetes mellitus type 2 uric acid stones were predominated (74.3%), significantly exceeding calcium oxalate (15.1%) and calcium phosphate (10.6%) stones. In the general population of patients with urolithiasis, hypercalciuria, hyperuricosuria, hyperuricemia and hypomagnesiuria was detected in 60.4%, 42.6%, 26.7% and 43.5% of cases, respectively. In patients with concomitant diabetes mellitus type 2, hypercalciuria, hyperuricosuria, hyperuricemia was observed in 9.4%, 26.7% and 42.5%, respectively. In 60.3% of patients with diabetes mellitus type 2 marked acidity of the morning urine was detected (pH<6.0). CONCLUSION: Correction of metabolic disorders in patients with urinary stone disease and diabetes mellitus type 2 should be aimed at increasing of urine pH and reducing the level of uric acid in the blood and urine.

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.