Aspectos biomoleculares de la prevención de la litogénesis biliar de colesterol / Biomolecular aspects of biliary cholesterol lithogenesis prevention

Introducción: La litogénesis biliar, proceso de sobresaturación de colesterol en la bilis vesicular, es prevenible. Objetivo: Describir las nuevas evidencias biomoleculares de la litogénesis biliar de colesterol como base de la futura terapia preventiva de la litiasis vesicular. Método: Se realizó una revisión sistemática y crítica de las evidencias de impacto sobre la litogénesis biliar. Se consultaron artículos publicados entre 2015-2020 en las bases de datos PubMed, Medline, SciELO, LILACS y Elsevier. Resultados: Se recuperaron evidencias actuales de los mecanismos biomoleculares relacionados con las futuras terapias preventivas de la litiasis vesicular, propuestos como fundamentos teóricos. Conclusiones: La descripción actualizada de la litogénesis biliar de colesterol, con los nuevos conceptos biomoleculares incorporados, aporta a su comprensión el papel de los genes de receptores nucleares, la intervención de estos últimos y de los transportadores de la secreción biliar. Dirigida a médicos generales, cirujanos, gastroenterólogos y fisiólogos, la descripción actualizada de La litogénesis biliar impacta como nuevo paradigma con los conceptos biomoleculares que intervienen en pro de su prevención(AU)

Introduction: Biliary lithogenesis is a preventable process of cholesterol supersaturation in gallbladder bile. Objective: Describe the new biomolecular evidence of biliary cholesterol lithogenesis serving as a basis for future preventive therapy for gallbladder lithiasis. Methods: A systematic critical review was conducted of impact evidence about biliary lithogenesis. The papers consulted were published in the databases PubMed, Medline, SciELO, LILACS and Elsevier from 2015 to 2020. Results: Current evidence was retrieved of biomolecular mechanisms proposed as theoretical foundations for future preventive therapies for gallbladder lithiasis. Conclusions: Intended for general practitioners, surgeons, gastroenterologists and physiologists, the updated description of biliary lithogenesis including the role of nuclear receptors, biliary lipid transporters and the biological value of enterohepatic circulation in the integrity and functioning of the hepatobiliary system as regulators of the cholesterol mechanism, makes an impact as a new paradigm with the biomolecular concepts involved in biliary lithogenesis prevention(AU)

Can SFR (stone free rate) be used as a preventive method for recurrence? medical management of residual fragments / ¿Se puede utilizar la tasa libre de litiasis como método preventivo de recurrencia? Manejo médico de fragmentos residuales

OBJECTIVE: To determine if the stone free rate (SFR) can be used as a preventive method for urolithiasis recurrence and to describe which would be the best medical management of residual fragments. METHODS: Narrative overview of the most relevant articles published in PubMed and Scopus database about this subject, together with the experiences of personal practice. RESULTS: Residual fragments, when ≤4 mm, sometimes are included in the SFR definition. Most reports shown that these fragments may growth and cause complications and re-intervention when found in the follow-up of the patient that underwent any endourological procedure. The majority of the publications found show that the residual fragment medical management is necessary to assure a lower recurrence rate. CONCLUSION: Assuring a SFR can serve as a preventive method for recurrence, but not alone but in combination with medical therapy. Medical therapy is important in the follow-up and personalized for each patient. Drug therapy must be promoted if the patient continues to have the urolithiasis risk factors despite the dietary objectives have been reached

OBJETIVO: Determinar si la tasa libre de litiasis se puede utilizar como un método preventivo de la recurrencia y describir cual sería el mejor manejo médico de los fragmentos residuales. MÉTODOS: revisión narrativa de los artículos publicados en Pubmed y Scopus sobre este tema, así como la experiencia personal. RESULTADOS: Los fragmentos residuales, cuando son de menos de 4 mm, a menudo están incluidos en el concepto de tasa libre de litiasis. La mayoría de artículos demuestran que estos fragmentos pueden crecen y generar complicaciones e re-intervenciones cuando son encontrados durante el seguimiento de pacientes que han recibido un tratamiento endourologico. La mayoría de publicaciones encontradas que en los fragmentos residuales el manejo medico es necesario para disminuir la tasa de recurrencias. CONCLUSIONES: Asegurarse de tener una tasa libre de litiasis baja puede funcionar como método preventivo de recurrencia, junto con el tratamiento médico. EL tratamiento médico es importante en el seguimiento de estos pacientes y debe ser personalizado por paciente. Los tratamientos farmacológicos deben ser utilizados en caso de pacientes con riesgo persistente de litiasis aunque el tratamiento dietético este establecido

Eficacia del sellante de fibrina-colágeno para reducir la incidencia de fístulas biliares tras la exploración laparoscópica de la vía biliar / Efficacy of fibrin-collagen sealant for reducing the incidence of biliary fistulae after laparoscopic exploration of the bile duct

No disponible

Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.

Efficacy of bladder irrigation and surveillance program in prevention of urinary tract infections and bladder calculi in children with an ileocystoplasty and bladder neck repair.

PURPOSE: In children with bladder augmentation and particularly in those with bladder neck repair (BNR), urinary tract infections (UTI) and bladder calculi are a recognised problem. Bladder irrigation potentially prevents these complications. Our aim was to investigate the efficacy of bladder irrigation supported by a surveillance program in prevention of UTI and bladder calculi in these children. METHODS: A cohort of children subjected to ileocystoplasty with a stoma for clean intermittent self catheterisation with or without BNR was retrospectively analysed. The children were subjected to bladder irrigation and monitored by Clinical Nurse Specialists (CNS) according to a protocol. Patients' demographics, treatment methods and postoperative management were reviewed. Compliance to bladder irrigation was assessed with questionnaires. UTI recurrence and bladder calculi during follow-up were assessed. RESULTS: 28 children were included in this study. The median follow-up was 48 months (range 6-87). Compliance could be assessed in all children, except in one child (3.5%). There was no recurrent UTI reported, bladder calculi occurred in two children (7%). CONCLUSION: Our bladder irrigation regime resulted in a low incidence of calculi by preventing recurrent UTI. The surveillance program resulted in high compliance rates in children with an augmented bladder with or without BNR.

The role of polymer nanosurface roughness and submicron pores in improving bladder urothelial cell density and inhibiting calcium oxalate stone formation.

Synthetic polymers have been proposed for replacing resected cancerous bladder tissue. However, conventional (or nanosmooth) polymers used in such applications (such as poly(ether) urethane (PU) and poly-lactic-co-glycolic acid (PLGA)) often fail clinically due to poor bladder tissue regeneration, low cytocompatibility properties, and excessive calcium stone formation. For the successful reconstruction of bladder tissue, polymer surfaces should be modified to combat these common problems. Along these lines, implementing nanoscale surface features that mimic the natural roughness of bladder tissue on polymer surfaces can promote appropriate cell growth, accelerate bladder tissue regeneration and inhibit bladder calcium stone formation. To test this hypothesis, in this study, the cytocompatibility properties of both a non-biodegradable polymer (PU) and a biodegradable polymer (PLGA) were investigated after etching in chemicals (HNO(3) and NaOH, respectively) to create nanoscale surface features. After chemical etching, PU possessed submicron sized pores and numerous nanometer surface features while PLGA possessed few pores and large amounts of nanometer surface roughness. Results from this study strongly supported the assertion that nanometer scale surface roughness produced on PU and PLGA promoted the density of urothelial cells (cells that line the interior of the bladder), with the greatest urothelial cell densities observed on nanorough PLGA. In addition, compared to respective conventional polymers, the results provided evidence that nanorough PU and PLGA inhibited calcium oxalate stone formation; submicron pored nanorough PU inhibited calcium oxalate stone formation the most. Thus, results from the present study suggest the importance of nanometer topographical cues for designing better materials for bladder tissue engineering applications.

Are new-generation bisphosphonates effective for the inhibition of calcium oxalate stone formation in a rat model?

BACKGROUND: The effects of bisphosphonates on prophylaxis of stone formation are unclear. We evaluated the outcome of two new-generation bisphosphonates in a lithogenic rat model. METHODS: 36 male rats were divided into three groups of 12 animals each. Both calcium and creatinine levels of plasma and urine were measured. Zinc discs of about 40 mg each were surgically placed into the bladder. The first group received no treatment and the second and third groups were treated with an intraperitoneal injection of weekly clodronate (20 mg/kg) and zoledronic acid (7.5 microg/kg), respectively. At the end of the 8th week, the weight increase in discs and biochemical changes were analyzed comparatively. RESULTS: The mean weight of discs in the control, clodronate and zoledronic acid groups was 109.65 +/- 80.97, 79.82 +/- 17.99 and 72.91 +/- 19.29 mg, respectively (p > 0.05). The percentage increase in weight of discs was 164% for control, 90% for clodronate and 71% for the zoledronic acid group. The increase of urinary calcium level in the zoledronic acid group was lower than the others (p < 0.05). CONCLUSIONS: When considering the percentage increase in weight of discs, the difference between control and bisphosphonate groups support the idea that these drugs may have a preventive role in stone formation.

Developing a strategy to reduce the high morbidity of patients with long-term urinary catheters: the BioMed catheter research clinic.

OBJECTIVE: To assess the idea of managing patients having problems with long-term catheterization (LTC, normally used when all other methods of bladder management have failed or are unsuitable) in a dedicated clinic, to present a prospective analysis of consecutive new patients attending between February 2002 and October 2006, and to establish the incidence of bladder stones in patients who have recurrent catheter encrustation and blockage. PATIENTS AND METHODS: Patients treated with LTC are a large heterogeneous group, mainly consisting of elderly people who have chronic disabilities, and catheter-associated complications occur in > 70% of them. In all, 260 consecutive new patients having problems with LTC were assessed; the evaluation consisted of basic demographics, a detailed history, clinical examination, urine analysis and flexible cystoscopy (FC) via the catheterization route. Patients with bladder stones were screened with FC for recurrence of stones at 3, 6 and 12 months after treatment. RESULTS: In all, 117 men and 143 women (mean age 67.7 years, range 23-97) were assessed; 147 (55.5%) had catheter encrustation. FC showed that 66 of the 147 patients (45%) had bladder stones. Forty-eight patients (73%) were successfully treated at the same clinic appointment and their stones were removed with the help of a tip-less stone basket. Eighteen patients (27%) were referred for inpatient treatment of bladder stones under general anaesthesia. Twenty of 66 patients with bladder stones (30%) formed recurrent bladder stones at a mean (range) follow-up of 8.1 (3-18 months). In addition, 36 patients had successful insertion of suprapubic catheter (SPC) under local anaesthetic in the clinic, and 11 were referred for SPC insertion under general anaesthesia. Two patients were diagnosed with bladder transitional cell carcinoma. CONCLUSION: The introduction of a dedicated catheter clinic, equipped with facilities such as FC and a hoist, enables patients to be treated in an environment that meets their needs and potentially reduces the risk of more complex stone removal and catheter problems at a later date. It can also act as a potential source of data for use in research and development. A significant proportion (45%) of patients with catheter encrustation and blockage had formed bladder stones. Our study provides a rationale for FC of all such patients to detect and remove stones.

Effects of low-molecular-weight polyguluronate sulfate on experimental urolithiasis in rats.

Urinary macromolecules, especially glycosaminoglycans (GAGs), have attracted great interest as promising inhibitors of urinary stone formation. As an analogue of GAGs, low-molecular-weight polyguluronate sulfate (LPGS) with strong polyanionic nature was prepared by chemical modification of brown algae extract. The effects of LPGS both on ethylene glycol-induced nephrolithiasis and Zinc disc implant-induced urinary bladder stone formation in Wistar rats were evaluated, and its acute toxicity in Kunming mice and Wistar rats were also investigated. The contents of renal oxalate and calcium in ethylene glycol-induced nephrolithiasic rats were decreased significantly from 5.01 +/- 0.96 to 3.26 +/- 1.31 mumol/g kidney (P < 0.01) and 20.11 +/- 4.60 to 11.83 +/- 3.54 mumol/g kidney (P < 0.01), respectively, after oral administration of LPGS at dose-level of 100 mg/kg. The renal crystal depositions and histopathological changes were reduced also. The formation of zinc disc implant-induced urinary bladder stones in rats was inhibited considerably after oral administration of LPGS at dose-levels of 50 mg/kg (P < 0.05) and 100 mg/kg (P < 0.01). The intravenous LD(50) and the oral maximum tolerance value of LPGS in mice are 6.29 and 25 g/kg, and in rats are 2.25 and 10 g/kg, respectively. These data show that LPGS has significant prevention effects both on nephrolithiasis and urinary bladder stone formation in rats, and negligible oral toxicity both in mice and rats. LPGS is a safe and promising drug candidate for the prevention of urolithiasis.

Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid.

The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO3) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO3) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis.

Bladder calculi after augmentation cystoplasty: risk factors and prevention strategies.

PURPOSE: Lower urinary tract reconstruction is an essential tool in the management of severely dysfunctional bladders in children. The incidence of calculi in augmented bladders has been reported in up to 50% of cases. We analyzed our experience with stone formation in this population to assess risk factors and outcomes. MATERIAL AND METHODS: We performed a retrospective cohort study of all patients who underwent bladder augmentation from 1988 to 2002 at our institution. Patient demographics, risk factors and management were abstracted from the medical record. RESULTS: A total of 105 patients (58 males and 47 females) were identified. Ileum, colon and stomach were used in 37, 18 and 50 patients, respectively. Median age was 8.0 years. Median followup was 8.4 years. A total of 12 patients (11%) were found to have bladder calculi. Ten patients with ileum (27%), 1 with colon (6%) and 1 with stomach (2%) formed stones. All patients had recurrent urinary tract infections. Nine patients were successfully treated with an endoscopic procedure. Four patients (33%) formed recurrent stones despite saline bladder irrigations. One patient had multiple recurrences but is now stone-free on a daily regimen of 20% urea instillation. CONCLUSIONS: Augmentation cystoplasty carries an overall low risk of bladder calculi. Gastrocystoplasty had a significantly lower rate of stone formation than augmentation with ileum and colon. Urinary tract infection is an independent risk factor for stone formation. Endoscopic management is safe and effective in the majority of patients and it may be facilitated by a percutaneous access. Recurrent stones form in some patients despite aggressive medical management.

Bladder management and risk of bladder stone formation in spinal cord injured patients.

PURPOSE: We determined by statistical analysis whether method of management is associated with risk of bladder stone formation in spinal cord injured patients. MATERIALS AND METHODS: A retrospective cohort study was performed of 457 patients admitted to Stoke Mandeville Hospital Spinal Injuries Center between 1985 and 1990 with more than 6 months of followup. Analysis included Cox regression and Poisson regression. RESULTS: Relative to those patients treated with intermittent self-catheterization, the hazard ratio was 10.5 (p <0.0005, 95% confidence interval 4.0-27.5) for patients with suprapubic catheters and it was 12.8 (p <0.0005, 95% confidence interval 5.1-31.9) for those with indwelling urethral catheters. The absolute annual risk of stone formation in patients with a catheter was 4% compared with 0.2% for those on intermittent self-catheterization. However, having formed a stone, the risk of forming a subsequent stone quadrupled to 16% per year. Bladder stones were no more likely to form in patients with suprapubic catheters compared to those with indwelling urethral catheters (hazard ratio 1.2, p = 0.6). CONCLUSIONS: In spinal cord injured patients long-term catheterization is associated with a substantial increased risk of bladder stone formation. This increased risk occurs independently of age, sex and injury level. Degree of injury (complete or incomplete) was considered in the model. Catheter type (suprapubic or urethral) did not change this risk significantly if at all.

Bladder stones following SCI in the Sprague-Dawley rat.

OBJECTIVE: To develop a spinal cord injury (SCI) animal model for the study of bladder stones and compare this model with a non-SCI animal model. METHODS: Small pieces of catheters were implanted into the bladders of Sprague-Dawley rats as a nidus for bladder stone formation. Three weeks later, the rats underwent an SCI surgery (SCI transection or sham SCI). Control rats had SCI surgery, but no catheters were implanted into their bladders. MAIN OUTCOME MEASURES: Bladder stone number, weight, and composition were determined in two groups of SCI and sham SCI animals: Group A (recent spinal shock: 2 weeks post-SCI/sham SCI surgery) and Group B (out of spinal shock: 3 weeks to 3 months post-SCI/sham SCI surgery). A chi2 test was used to compare the incidence of bladder stones in SCI vs sham SCI animals. A Student t test was used to compare the weight of bladder stones in the 2 groups. RESULTS: Group A (recent spinal shock): Of the 20 SCI rats, 8 (40%) had stones. None of the sham SCI rats with implanted catheters (n = 5) had stones (0%). Group B (out of spinal shock): All 6 of the SCI rats with implanted catheters had stones (100%). Of the 10 sham SCI animals with implanted catheters, 3 (30%) had stones. Stones were more common in the SCI rats than in the sham SCI rats (chi2(1) = 4.9, P < 0.05). The mean weight of the bladder stones in SCI rats (42.2 +/- 16.3 mg) was greater than that in sham SCI rats (5.4 +/- 1.5 mg) (P < 0.01). Group C (controls: SCI surgery, but no catheter implanted): At 3 weeks post-SCI, control rats had no stones (n = 7); control rats at 3 months post-SCI also had no stones (n = 9). Stone composition in the 3 sham SCI animals was calcium apatite (90%) and calcium oxylate (10%). In the 14 SCI rats, 10 had struvite stones (100%), 1 had struvite (70%) and carbonate apatite (30%) stones, 1 had brushite (100)% stones, and 2 had carbonate apatite (> 90%) stones. CONCLUSION: Bladder stones occurred earlier and more frequently and attained a larger size in SCI rats with catheters compared with sham SCI rats with catheters. There were no stones in SCI rats without catheter implants, even at 3-month follow-up. The bladder stone composition in SCI rats was similar to that in humans with SCI. The Sprague-Dawley rat model appears to be an excellent animal model for the study of bladder stones following SCI.

A method to minimize indwelling catheter calcification and bladder stones in individuals with spinal cord injury.

Indwelling catheters are a common tool of bladder management in persons with high-level spinal cord injury who are unable to intermittently catheterize their bladders. Indwelling catheters are used to prevent bladder overdistension, which can trigger autonomic dysreflexia in those with injuries at or above T6. Unfortunately, indwelling catheters are prone to encrustation and can lead to the formation of bladder stones that can block the catheter and cause autonomic dysreflexia. We found that weekly catheter changes dramatically reduced catheter encrustation and stones in 2 individuals who had a history of recurrent stones despite various accepted interventions. We describe the clinical course and impact of this method in each case.

Bladder calculi in augmentation cystoplasty in children.

OBJECTIVES: To determine the best preventive strategies for bladder calculi in children with an augmented bladder, the risk factors and prevention strategies for urolithiasis were evaluated. METHODS: The records of 89 patients following augmentation cystoplasty were reviewed to assess the results of augmentation cystoplasties and in particular the formation and prevention of calculi. RESULTS: The median follow-up was 4.9 years after augmentation. Most patients (71) had an ileocystoplasty. Bladder calculi occurred in 14 of the 89 patients (16%) and recurred in 4 patients. Girls had a higher incidence of urolithiasis. Other risk factors were cloacal malformations, vaginal reconstructions, anal atresia, clean intermittent catheterization problems and retention, bladder neck surgery, and symptomatic urinary tract infections. CONCLUSIONS: Subgroups with cloacal malformations, vaginal reconstructions, ureter reimplantation, and bladder neck surgery were identified that have an increased risk for stone formation and therefore warrant special care in the follow-up after augmentation. This care should include clear emphasis on the role of treating symptomatic urinary tract infections, especially in patients with cloacal malformations and vaginal reconstructions. Girls have a higher incidence of bladder calculi than boys.

Aspectos celulares e moleculares da interaçäo entre cristais de oxalato de cálcio e células tubulares renais / Cell and molecular aspects of the interaction between calcium oxalate crystals and the kidney tubular cells

Nos últimos anos o emprego de técnicas de biologia celular e molecular permitiu que conceitos acerca da origem da litíase do trato urinário mudassem consideravelmente. A interaçao entre cristais de oxalato de cálcio e o epitélio tubular renal exerce importante papel na gênese dos cálculos renais. Os aspectos envolvendo a adesao destes cristais às células tubulares, desencadeando internalizaçao dos mesmos e uma resposta celular proliferativa expressiva sao aqui revistos e podem representar um novo caminho para a prevençao e o tratamento da nefrolitíase.

Controlling influence of phosphocitrate in vitro and in vivo on calcium oxalate crystal formation and growth.

Calcium oxalate (CaOx) crystallization in the presence of phosphocitrate (PC) was studied by both in vitro and in vivo techniques. Crystals of the monohydrate (COM) and the dihydrate (COD) forms were generated under controlled conditions in a silica gel matrix. Our data indicated only COD crystals formed when PC was present, inferring that the COD to COM transformation was being impeded. COD crystals were smaller in size than controls and there was evidence of interpenetral twinning. An in vivo study using a rat bladder implant model noted similar findings. Scanning electron microscopy (SEM) revealed that implants recovered from PC treated rats had primarily COD crystals deposited, whereas both the surface and inner layers of encrusted implants from normal rats contained predominantly COM crystals. Infrared (IR) analysis confirmed the visual findings indicating quantitatively that there was a higher proportion of COD present on the implants recovered from the treated rats than in the controls. It is concluded that although total CaOx crystallization cannot be eliminated by PC, its action could assist in reducing the harmful nature of such crystallites in the urine.

Tamm-Horsfall mucoprotein reduces promotion of calcium oxalate crystal aggregation induced by urate in human urine in vitro.

1. Increasing the concentration of dissolved urate promotes calcium oxalate crystallization in urine from which Tamm-Horsfall mucoprotein, an inhibitor of calcium oxalate crystal aggregation, has almost completely been removed. This study aimed to determine whether the effect of urate could be reduced or abolished by a physiological concentration of Tamm-Horsfall mucoprotein. This was approached in two ways. 2. The effect of Tamm-Horsfall mucoprotein on calcium oxalate crystallization induced by urate was tested in ultrafiltered (10 kDa) urine samples from 10 healthy men. Tamm-Horsfall mucoprotein (35 mg/l) was added to half of each specimen, the urate concentration was increased by the addition of sodium urate solution and crystallization was induced by a standard load of oxalate. The remainder of each urine specimen was used as a control; these specimens were treated with an identical amount of urate solution, but contained no Tamm-Horsfall mucoprotein. Tamm-Horsfall mucoprotein had no effect on the urinary metastable limit or on the deposition of calcium oxalate, but significantly reduced the size of the particles precipitated. 3. The effect of increasing the urate concentration in the presence of Tamm-Horsfall mucoprotein was tested. Tamm-Horsfall mucoprotein (35 mg/l) was added to 10 ultrafiltered urine samples as before, the samples were divided, and the concentration of urate was increased in half of each specimen. Compared with the control to which no urate was added, urate significantly reduced the amount of oxalate required to induce spontaneous calcium oxalate nucleation and increased the median volume and the particle size of the material deposited.(ABSTRACT TRUNCATED AT 250 WORDS)