Recent advances on the mechanisms of kidney stone formation (Review).

Kidney stone disease is one of the oldest diseases known to medicine; however, the mechanisms of stone formation and development remain largely unclear. Over the past decades, a variety of theories and strategies have been developed and utilized in the surgical management of kidney stones, as a result of recent technological advances. Observations from the authors and other research groups suggest that there are five entirely different main mechanisms for kidney stone formation. Urinary supersaturation and crystallization are the driving force for intrarenal crystal precipitation. Randall's plaques are recognized as the origin of calcium oxalate stone formation. Sex hormones may be key players in the development of nephrolithiasis and may thus be potential targets for new drugs to suppress kidney stone formation. The microbiome, including urease­producing bacteria, nanobacteria and intestinal microbiota, is likely to have a profound effect on urological health, both positive and negative, owing to its metabolic output and other contributions. Lastly, the immune response, and particularly macrophage differentiation, play crucial roles in renal calcium oxalate crystal formation. In the present study, the current knowledge for each of these five aspects of kidney stone formation is reviewed. This knowledge may be used to explore novel research opportunities and improve the understanding of the initiation and development of kidney stones for urologists, nephrologists and primary care.

Urolithiasis and cystitis associated with Staphylococcus delphini group A and mortality in post-weaning mink kits (Neovison vison).

Mortality of mink kits represents a significant loss to production. However, causes of post-weaning mortality in mink kits in modern Danish mink production systems are still relatively poorly documented. We performed a cross-sectional mortality study on eight Danish mink farms including 1893 post mortem examinations of mink kits found dead or euthanized. We assessed the prevalence of cystitis and urolithiasis leading to mortality. Gross pathological findings as well as animal characteristics were recorded and associations with post mortem microbiology (using culture and MaldiTof-MS Vitek MS system) were investigated. Cystitis and/or urolithiasis were associated with death in 33 % (n = 476) and 37 % (n = 166) of the examined mink kits in 2015 and 2017. On farm level, the prevalence of cystitis and/or urolithiasis leading to mortality varied from 0.25 % to 1.27 % with a low overall mortality of 0.9-4.5 %. The bacterial agent most frequently isolated in post mortem bladder swabs from mink with a post mortem diagnosis of urolithiasis and cystitis was Staphylococcus delphini group A (51/283) with a significant (p < 0.0001, CI = [19.5;4745.7]) association to gross pathological findings in the urinary tract. Staphylococcus delphini group A was cultured from 70 % of the skin swabs obtained from apparently healthy mink euthanized at pelting (n = 222). In conclusion urinary tract disease (cystitis and urolithiasis) was the most prevalent post mortem diagnosis during the growth period and was associated with Staphylococcus delphini group A.

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.

The microbiome of the urinary tract--a role beyond infection.

Urologists rarely need to consider bacteria beyond their role in infectious disease. However, emerging evidence shows that the microorganisms inhabiting many sites of the body, including the urinary tract--which has long been assumed sterile in healthy individuals--might have a role in maintaining urinary health. Studies of the urinary microbiota have identified remarkable differences between healthy populations and those with urologic diseases. Microorganisms at sites distal to the kidney, bladder and urethra are likely to have a profound effect on urologic health, both positive and negative, owing to their metabolic output and other contributions. Connections between the gut microbiota and renal stone formation have already been discovered. In addition, bacteria are also used in the prevention of bladder cancer recurrence. In the future, urologists will need to consider possible influences of the microbiome in diagnosis and treatment of certain urological conditions. New insights might provide an opportunity to predict the risk of developing certain urological diseases and could enable the development of innovative therapeutic strategies.

Secondarily infected nonstruvite urolithiasis: a prospective evaluation.

OBJECTIVE: To characterize patients who form nonstruvite stones associated with infection (secondarily infected calculi), and to define the bacteria associated with these. MATERIALS AND METHODS: Patients undergoing percutaneous nephrolithotomy were prospectively recruited. Medical records were reviewed, and stones were analyzed using micro computed tomography and infrared spectroscopy. A fragment of each stone was sent for bacterial culture. Patients were categorized by stone culture results (SC ±) and the presence of struvite (ST ±). The Fisher exact test was used for comparison of proportion. Sterility of intraoperative SC was established with independently collected controls. RESULTS: In total, 125 patients were enrolled: 24 SC+/ST-, 19 SC+/ST+, and 82 SC-/ST-. Proportions of patients with prior urologic surgery, diabetes, and immunodeficiency were similar between groups. Patients with neurogenic bladder were more likely to have SC+/ST+ stones or SC+/ST- stones than SC-/ST- stones (26% vs 8% vs 0%, respectively; P <.01). Among patients with metabolic evaluations, hypocitraturia was found in 31.6% (6 of 19) SC+/ST- patients, 46.7% (7 of 15) SC+/ST+ patients, and 26.0% (19 of 73) of SC-/ST- patients (P = .28). Approximately 40% of cultured organisms in the secondarily infected calculi possessed urease and another 40% citrate lyase activities. CONCLUSION: Secondarily infected stones were detected in approximately 20% of this surgical cohort and may be more common than previously appreciated. Neurogenic bladder appeared to predispose patients to either struvite or secondarily infected stones. The role of bacterial infection in stone formation is unclear but may include alteration of urinary components, acting as a nidus for crystallization, or inducing inflammation.

[Use of furamag to prevent inflammatory complications during endoscopic operations in patients with benign prostatic hyperplasia and urolithiasis].

AIM: To improve surgical results in patients with benign prostatic hyperplasia (BPH) and urolithiasis (UL) and to evaluate the efficacy of Furamag used as an agent to prevent infectious and inflammatory complications. SUBJECTS AND METHODS: Seventy-two patients with BPH (n = 36; Group 1) and UL (n = 36; Group 2) were examined. Within each group, the patients were divided into two subgroups: A) those in whom no preventive measures were taken during endoscopic operations; B) those who received Furamag as a preventive agent. The preventive efficacy was evaluated from the urine microbial spectrum and renal microcirculatory values. RESULTS: The preventive use of Furamag could achieve better urine sanitation, normalize renal microcirculatory values, and reduce the incidence of postoperative complications. CONCLUSION: The use of Furamag to prevent intravesical obstruction (IVO) during transurethral prostatic resection and UL reduces the incidence of IVO, results in less noticeable renal microcirculatory disorders, and accordingly assists in lowering the incidence of postoperative complications.

Presentaciones efectivas en medicina El arte de comunicar y transmitir: diez recomendaciones / Effective Presentations in Medicine. The Art of Communication and Transmission: Ten Recommendations

Para lograr una comunicación efectiva durante una conferencia o presentación, es necesario seguir reglas simples, que incluyen la preparación de la conferencia con el auditorio en mente y con la definición de un mensaje específico para dejar a la audiencia. Debe capturarse pronto la atención del público y todas las acciones posteriores deben ir encaminadas a mantenerla. Los textos deben ser precisos y con tamaños fácilmente visibles, las diapositivas deben ofrecer buen contraste, con fondos sólidos y simples y deben evitarse las animaciones excesivas. Al cierre de la conferencia, las conclusiones y la sesión de preguntas ofrecen la oportunidad invaluable de reforzar el mensaje que se quería dejar.

To communicate effectively during a lecture or presentation it is necessary to follow simple rules, including the preparation of the conference with the audience in mind and with the definition of a specific message to leave the audience. The public's attention should be quickly captured and all subsequent actions should aim to keep it. The text must be accurate and sizes easily visible, the slides should provide good contrast with solid and simple backgrounds and should avoid excessive animations. At the close of the conference, the conclusions and question session offers the invaluable opportunity to reinforce the desired message.

Use of a rectus abdominis muscle flap to repair urinary bladder and urethral defects in a dog.

CASE DESCRIPTION: An 11-month-old female dog was evaluated because of a 3- to 4-day history of stranguria and hematuria. CLINICAL FINDINGS: Rectal and vaginal examination and abdominal radiography revealed a large (4 x 2 cm), firm, ovoid object in the area of the pelvic inlet, between the vagina and colon. TREATMENT AND OUTCOME: Surgical exploration revealed an abscess and moderate amount of seropurulent fluid in the left caudal abdominal quadrant. A large urethrolith (3.7 x 2.0 x 1.5 cm) was evident in the proximal portion of the urethra. The urethrolith was associated with a 3 x 1-cm area of necrosis in the ventral aspect of the proximal portion of the urethra and a 3 x 3-cm area of necrosis in the area of the bladder trigone. The necrotic areas were débrided, and the defect was repaired with an axial pattern flap constructed from the rectus abdominis muscle. During a follow-up examination 2.5 years after surgery, the dog was clinically normal with no history of urinary incontinence. During rigid cystoscopy, the ure-thral mucosa appeared grossly normal, and there was no evidence of stricture. CLINICAL RELEVANCE: Findings suggested that axial pattern flaps constructed from the rectus abdominis muscle flap may be useful in reconstructing large urinary bladder and urethral defects.

Staphylococcus-induced urolithiasis in estrogen-treated ovariectomized nude mice.

Nine of 24 ovariectomized nude mice developed ulcerative skin lesions 28 d after implantation with human breast cancer cells and slow-release estrogen pellets. Aerobic culture of samples from the skin lesions yielded Staphylococcus intermedius. By day 45 postimplantation, all mice displayed ulcerative skin lesions, and 5 mice exhibited hunched posture, listless behavior, cyanosis, anorexia, and dehydration. This subset was euthanized but not necropsied. When additional animals became moribund, the investigator elected to end the study at day 51. At necropsy, all 20 but 1 had cystitis and urolithiasis, characterized by relatively large struvite stones and crystals that had filled the urinary bladders of the research animals and caused severe thickening of the bladder walls. Gram-positive cocci were observed microscopically in both the kidneys and bladders of the necropsied animals. Spontaneous urolithiasis has not previously been documented to occur in association with infection of female nude mice by S. intermedius.

Comparison of three techniques for the diagnosis of urinary tract infections in dogs with urolithiasis.

OBJECTIVES: To identify an appropriate sampling technique(s) to accurately detect the bacteria causing urinary tract infections in dogs with urolithiasis. METHODS: Twenty-one dogs with urolithiasis were included in the study. Three types of samples were taken from each dog. Urine was collected by cystocentesis, and a urinary bladder mucosal biopsy and urolith were retrieved during cystotomy. The samples were then cultured on blood agar and MacConkey's agar to identify the bacteria associated with urinary tract infections. RESULTS: Bacterial urinary tract infection was found in 16 cases (76.19 per cent). The most prevalent bacteria found to cause urinary tract infection were Escherichia coli (n=7), followed by coagulase-positive Staphylococcus species (n=4), Klebsiella pneumoniae (n=2), Pseudomonas aeruginosa (n=2) and Proteus mirabilis (n=1). In the case of a positive urine culture, the same bacteria were also cultured from the urinary bladder mucosal biopsy alone or from both the urinary bladder mucosal biopsy and urolith. However, in the case of a negative urine culture, bacteria were found to be present in the urinary bladder mucosal biopsy or urolith cultures in 23.81 per cent of dogs. The uroliths that gave positive culture results were either infection-induced uroliths composed of struvite and calcium carbonate phosphate, ammonium acid urate only or metabolic uroliths composed of calcium oxalate and calcium phosphate, or calcium phosphate only. All the uroliths that gave negative culture results were metabolic uroliths composed of calcium oxalate and/or calcium phosphate, and uric acid and calcium phosphate. CLINICAL SIGNIFICANCE: When the culture from the urine obtained by cystocentesis is negative, cultures of urinary bladder mucosal biopsy and urolith are recommended in dogs with urolithiasis in order to accurately assess the microbiological status of the urinary tract.