Management of urinary stones: state of the art and future perspectives by experts in stone disease.

AIM: To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up:  Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies. PROPHYLAXIS: Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched. FUTURE RESEARCH: Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.

Cystine Renal Calculi: New Aspects Related to Their Formation and Development.

Background: Crystallization experiments of renal-calculi-forming compounds (calcium oxalate, calcium phosphates, uric acid) are normally performed by monitoring these processes during periods of time similar to the residence of urine inside the kidney. Nevertheless, cystine requires high supersaturation for its crystallization, and most experiments last for longer periods. It must be considered that at high supersaturation, the inhibitors of crystalline development have poor effects. Methods: The induction time of crystallization (ti) of cystine in experimental conditions similar to those of the formation of cystine renal calculi and the effect of different cystine-binding thiol agents was determined through turbidimetric measurements. We also studied the macro- and microstructure of 30 cystine kidney stones through stereoscopic microscopy and scanning electron microscopy. Results: Under the studied conditions, the ti in absence of crystallization inhibitors was 15 min, and the presence of 9 mM of penicillamine, tiopronin, or N-acetylcysteine totally inhibited crystallization, as their effects relate to the formation of complexes with cystine, although N-acetylcysteine also delayed cystine crystalline development and modified cystine crystal morphology. Cystine stones have traditionally been classified as smooth and rough. The study of their structure shows that all of them begin their formation from a few crystals that generate a compact radial structure. Their subsequent growth, depending on the renal cavity where they are located, gives rise to the rough structure in the form of large blocks of cystine crystals or the smooth structure with small crystals. Conclusions: To prevent the development of cystine renal stones, the formation of small crystals must be avoided by reducing urinary cystine supersaturation, with N-acetylcysteine being the most effective among the studied cystine-binding thiol agents. Also, the removal of cystine crystals through increased water intake and physical activity can be a very important preventive measure.

Daily phytate intake increases adiponectin levels among patients with diabetes type 2: a randomized crossover trial.

AIM: Adiponectin, a major adipokine secreted by adipose tissue, has been shown to improve insulin sensitivity. Myo-inositol hexaphosphate (phytate; InsP6) is a natural compound that is abundant in cereals, legumes, and nuts that has demonstrated to have different beneficial properties in patients with diabetes type 2. METHODS: We performed a randomized crossover trial to investigate the impact of daily consumption of InsP6 on serum levels of adiponectin, TNF-alpha, IL-6, and IL-1beta in patients with type 2 diabetes mellitus (T2DM; n = 39). Thus, we measure serum levels of these inflammatory markers, classic vascular risk factors, and urinary InsP6 at baseline and at the end of the intervention period. RESULTS: Patients who consumed InsP6 supplements for 3 months had higher levels of adiponectin and lower HbA1c than those who did not consume InsP6. No differences were found in TNF-alpha, IL-6, and IL-1beta. CONCLUSION: This is the first report to show that consumption of InsP6 increases plasma adiponectin concentration in patients with T2DM. Consequently, our findings indicate that following a phytate-rich diet has beneficial effects on adiponectin and HbA1c concentrations and it could help to prevent or minimize diabetic-related complications.

Effect of theobromine on dissolution of uric acid kidney stones.

PURPOSE: Uric acid renal lithiasis has a high prevalence and a high rate of recurrence. Removal of uric acid stones can be achieved by several surgical techniques (extracorporeal shock wave lithotripsy, endoscopy, laparoscopy, open surgery). These stones can also be eliminated by dissolution within the kidneys, because the solubility of uric acid is much greater when the pH is above 6. At present, N-acetylcysteine with a urinary basifying agent is the only treatment proposed to increase the dissolution of uric acid stones. In this paper, we compare the effect of theobromine and N-acetylcysteine on the in vitro dissolution of uric acid calculi in artificial urine at pH 6.5. METHODS: The dissolution of uric acid renal calculi was performed in a temperature-controlled (37 °C) chamber. A peristaltic pump was used to pass 750 mL of synthetic urine (pH 6.5) through a capsule every 24 h. Stone dissolution was evaluated by measuring the change in weight before and after each experiment. RESULTS: N-acetylcysteine increased the dissolution of uric acid calculi, but the effect was not statistically significant. Theobromine significantly increased the dissolution of uric acid calculi. Both substances together had the same effect as theobromine alone. The addition of theobromine to a basifying therapy that uses citrate and/or bicarbonate is a potential new strategy for the oral chemolysis of uric acid stones. CONCLUSION: Theobromine may prevent the formation of new stones and increase the dissolution of existing stones.

Urinary stone diagnosis. Morphologic and composition analysis. / Diagnóstico de la litiasis renal a través del cálculo. Estudio morfocomposicional.

Analysis of urinary stones is an essential step in establishing the diagnosis and treatment of the stone patient. In fact, the need for an exhaustive study of the stones increases as the relationships between the type of stone and the etiological factors that predispose to this disease become evident. The enumeration (qualitative or quantitative) of the major components that make up the kidney stone (calcium oxalate monohydrate, calcium oxalate dihydrate, uric acid, calcium phosphates, cystine), which is obtained by the most commonly used analytical method, infrared spectroscopy (IR), is no longer enough to guide the urologist on the etiology of the disease. Only a detailed structural analysis and macro and micro components can provide key information on the etiology of the stone, and therefore, on the possible causes that have led to its formation. This study should conclude with a report that is provided to the Urologist. Obtaining this report involves a detailed study, sample by sample, which involves the systematic handling of stereoscopic microscopy, IR spectroscopy and scanning electron microscopy (SEM) with energy dispersive X-raymicroanalysis (EDAX).

El análisis de los cálculos urinarios es un paso esencial para establecer el diagnóstico y tratamiento del paciente litiásico. De hecho, la necesidad de un estudio exhaustivo de los cálculos aumenta a medida que se evidencian las relaciones entre la tipologíadel cálculo y los factores etiológicos que predisponen a esta enfermedad. La relación de los componentes mayoritario sque componen el cálculo renal (oxalato cálcico monohidrato, oxalato cálcico dihidrato, ácido úrico, fosfatos cálcicos, cistina), que se obtiene por el método analítico generalmente más utilizado, la espectroscopía infrarroja (IR), ya no es suficiente para orientar al urólogo sobre la etiología de la enfermedad. Únicamente un detallado análisis estructural y de macro y micro componentes permite aportar información clave sobre el origen del cálculo, y por tanto, de las posibles causas que han inducido a su formación. Este estudio debe concluir con un informe que se suministra al Urólogo. La obtención de este informe supone un estudio en detalle, muestra a muestra, que implica el manejo sistemático de microscopía estereoscópica, espectroscopía IR y microscopía electrónica de barrido (SEM) con microanálisis por energía dispersiva de rayos X (EDAX).

Reduction of ureteral stent encrustation by modulating the urine pH and inhibiting the crystal film with a new oral composition: a multicenter, placebo controlled, double blind, randomized clinical trial.

BACKGROUND: Encrustation of ureteral double J stents is a common complication that may affect its removal. The aim of the proposed study is to evaluate the efficacy and safety of a new oral composition to prevent double J stent encrustation in indwelling times up to 8 weeks. METHODS: A double-blinded, multicenter, placebo-controlled trial was conducted with 105 patients with indwelling double J stents enrolled across 9 public hospitals in Spain. The patients were randomly assigned (1:1) into intervention (53 patients) or placebo (52 patients) groups for 3 to 8 weeks and both groups self-monitored daily their morning urine pH levels. The primary outcome of analysis was the degree of stent ends encrustation, defined by a 4-point score (0 - none; 3 - global encrustation) using macroscopic and electron microscopy analysis of crystals, after 3 to 8-w indwelling period. Score was exponentially transformed according to calcium levels. Secondary endpoints included urine pH decrease, stent removal, and incidence of adverse events. RESULTS: The intervention group benefits from a lower global encrustation rate of stent ends than placebo group (1% vs 8.2%; p < 0.018). Mean encrustation score was 85.12 (274.5) in the placebo group and 18.91 (102.27) in the intervention group (p < 0.025). Considering the secondary end points, treated patients reported greater urine pH decreases (p = 0.002). No differences in the incidence of adverse events were identified between the groups. CONCLUSIONS: Our data suggest that the use of this new oral composition is beneficial in the context of ureteral double J indwelling by decreasing mean, as well as global encrustation. TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov under the name "Combined Use of a Medical Device and a Dietary Complement in Patient Urinary pH Control in Patients With an Implanted Double J Stent" with date 2nd November 2017, code NCT03343275, and URL.

Key Aspects of Myo-Inositol Hexaphosphate (Phytate) and Pathological Calcifications.

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine.

2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.

BACKGROUND: High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods. OBJECTIVE: To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2. METHODS: Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS). RESULTS: The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(C15H15O2N7) + H+]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal. CONCLUSION: DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.

[May renal lithiasis be really prevented? New trends and therapeutic tools.] / Se puede realmente prevenir la litiasis renal? Nuevas tendencias y herramientas terapéuticas.

Renal calculi are generally formed as a result of the combination of certain factors, some related to urine composition (concentration of lithogenic substances, deficiency of crystallization inhibitors, presence of heterogeneous nucleants) and others with renal morphology and anatomy (urinary tract stasis, low urodynamic efficiency cavities, morpho-anatomic deformations, renal papillary tissue lesions). In fact, the composition, macrostructure and microstructure of the calculus will clearly depend on the factors that have induced it. For this reason, the appropriate study and classification of the renal calculi simplifies the diagnosis and allows a more effective therapeutic approach since it can be oriented to directly correct the etiological factors responsible for stone formation. In this article, we review the main etiological factors involved in the formation of each type of calculus and the prophylactic measures that can be adopted for proper correction. The most frequent kidney stones have been classified into the following types: calcium oxalate monohydrate papillary calculi, calcium oxalate monohydrate non-papillary calculi, calcium oxalate dihydrate calculi, mixed hydroxyapatite/ calcium oxalate calculi, carboxyapatite/hydroxyapatite calculi, brushite calculi, struvite/carboxyapatite calculi, uric acid calculi, uric acid/calcium oxalate monohydrate calculi, and cystine calculi. Occasionally, however, the calculus is not available for study, in which case the only way forward is to use all available information (clinical history, life habits, radiological data), together with basic biochemical information, to identify and correct all etiological factors related to renal lithiasis that have been identified.

Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study.

Pathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification. This cross-sectional study evaluated the relationship between physiological levels of urinary phytate and heart valve calcification in a population of elderly out subjects. A population of 188 elderly subjects (mean age: 68 years) was studied. Valve calcification was measured by echocardiography. Phytate determination was performed from a urine sample and data on blood chemistry, end-systolic volume, concomitant diseases, cardiovascular risk factors, medication usage and food were obtained. The study population was classified in three tertiles according to level of urinary phytate: low (<0.610 µM), intermediate (0.61-1.21 µM), and high (>1.21 µM). Subjects with higher levels of urinary phytate had less mitral annulus calcification and were less likely to have diabetes and hypercholesterolemia. In the multivariate analysis, age, serum phosphorous, leukocytes total count and urinary phytate excretion appeared as independent factors predictive of presence of mitral annulus calcification. There was an inverse correlation between urinary phytate content and mitral annulus calcification in our population of elderly out subjects. These results suggest that consumption of phytate-rich foods may help to prevent cardiovascular calcification evolution.

Effects of polyphenols from grape seeds on renal lithiasis.

Nephrolithiasis is a complex disease that results from a combination of factors related to both urine composition and kidney morphoanatomy. Development of calcium oxalate monohydrate papillary calculi is linked to initial subepithelial calcification of renal papilla. Progressive tissue calcification depends on preexisting injury and involves reactive oxygen species. Many plant extracts that protect against oxidative stress manifest antilithiasic activity. Our study focused on determining the effects of polyphenols on a lithiasis rat model. Rats were pretreated with polyphenols and grape seed extracts, followed by posterior induction of hyperoxalosis via treatment with ethylene glycol plus NH4Cl. The concentrations of calcium and other elements in kidney were determined, along with histological examination of kidney and 24 h urine analysis. Significant differences were observed in the renal calcium content between the control plus ethylene glycol-treated group and the epicatechin plus ethylene glycol-treated, red grape seed extract plus ethylene glycol-treated, and white grape seed extract plus ethylene glycol-treated groups, with reductions of about 50%. The antioxidant activity of polyphenols extracted from red and white grape seeds may be critical in the prevention of calcium oxalate monohydrate papillary calculus formation, particularly if calculi are induced by lesions caused by cytotoxic compounds with oxidative capacity.

Characterization of deposits in patients with calcific tendinopathy of the supraspinatus. Role of phytate and osteopontin.

Calcific tendinopathy of the tendons of the rotator cuff is common in adults. These calcifications tend to be reabsorbed after a period of acute pain. This study evaluated the morphologic characteristics of calcific deposits and the participation of phytate and osteopontin (OPN) in their development. Calcific deposits were removed from 21 patients with calcific tendinopathy by ultrasound-guided needle puncture under local anesthesia. The removed deposits were evaluated by scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The amounts of calcium and phosphorus in the deposits were semi-quantitatively determined by energy dispersive X-ray analysis. Phytate was determined in 2 h urine samples, and OPN was extracted from a pool of deposits. The calcific deposits consisted of amorphous and poorly crystalline carbonated hydroxyapatite containing molecular water and organic matter. OPN was associated with the hydroxyapatite deposits. Phytate concentrations were significantly lower in the urine of patients with calcific tendinopathy than in healthy controls. The deficit in crystallization inhibitors such as phytate, and the presence of regulators such as OPN, may play important roles in the development of calcific tendinopathy.

On the origin of calcium oxalate monohydrate papillary renal stones.

Calcium oxalate monohydrate (COM) papillary calculi can be initiated by subepithelial calcification of the renal papillae. Hydroxyapatite disruption of the papillary epithelial layer can become the nidus of a COM papillary calculus. This study evaluated the causes of papillary tissue calcifications in 60 patients with calcium oxalate lithiasis, 30 with COM papillary and 30 with calcium oxalate dihydrate (COD) calculi. Urinary redox potential was higher in the COM than the COD group, suggesting that the former is more deficient in antioxidants due to increased oxidative stress. Urinary calcium was significantly higher in the COD group, whereas urinary oxalate was significantly higher in the COM group, suggesting a greater degree of oxidative injury of renal cells. Evaluations of their diets showed that both groups consumed low amounts of phytate-rich products. Of chronic diseases possibly associated with urolithiasis, only the prevalence of gastroduodenal ulcer differed significantly, being higher in the COM group and suggesting that epithelial lesions are common to gastroduodenal ulcers and COM papillary renal stones. Occupational exposure to cytotoxic products occurred in 47 % of the COM and 27 % of the COD group, but this difference was not statistically significant. These findings indicate that oxidative stress is associated with injury to papillary tissue and that this is the origin of intrapapillary calcifications. The continuation of this process is due to modulators and/or deficiencies in inhibitors of crystallization. Identifying and eliminating the causes of injury may prevent recurrent episodes in patients with papillary COM calculi.

Renal papillary calcification and the development of calcium oxalate monohydrate papillary renal calculi: a case series study.

BACKGROUND: The objective of this study is to determine in a case series (four patients) how calcified deposits in renal papillae are associated with the development of calcium oxalate monohydrate (COM) papillary calculi. METHODS: From the recently collected papillary calculi, we evaluated retrospectively patients, subjected to retrograde ureteroscopy, with COM papillary lithiasis. RESULTS: The COM papillary calculi were found to result from subepithelial injury. Many of these lesions underwent calcification by hydroxyapatite (HAP), with calculus morphology and the amount of HAP in the concave zone dependent on the location of the calcified injury. Most of these HAP deposits grew, eroding the epithelium covering the renal papillae, coming into contact with urine and starting the development of COM calculi. Subepithelial HAP plaques may alter the epithelium covering the papillae, resulting in the deposit of COM crystals directly onto the epithelium. Tissue calcification depends on a pre-existing injury, the continuation of this process is due to modulators and/or crystallization inhibitors deficiency. CONCLUSIONS: Since calculus morphology and the amount of detected HAP are dependent on the location and widespread of calcified injury, all types of papillary COM calculi can be found in the same patient. All patients had subepithelial calcifications, with fewer papillary calculi, demonstrating that some subepithelial calcifications did not further evolve and were reabsorbed. A high number of subepithelial calcifications increases the likelihood that some will be transformed into COM papillary calculi.

Origin and types of calcium oxalate monohydrate papillary renal calculi.

OBJECTIVES: Subepithelial hydroxyapatite calcification of renal papilla is thought to be involved in the formation of calcium oxalate monohydrate (COM) papillary calculi. To assess the mechanism of formation, we sought to correlate the fine structure of papillary renal calculi with specific pathophysiologic conditions and urinary alterations. METHODS: The study included 831 COM papillary renal calculi with established fine inner structures. A total of 24 patients with chronic stone formation were randomly selected, and their urine was collected and analyzed. The case history and lifestyle habits of these patients were obtained. RESULTS: The 831 papillary calculi could be classified into 1 of 4 main groups. Type I included small calculi in which COM columnar crystals begin to develop in the concave zone in close contact with papillary tissue. Type II calculi contained a hydroxyapatite core located in or near the concave zone. Type III consisted of calculi that developed on the tip of the papillae and in the concave zone, containing hydroxyapatite, calcified tissue, and calcified tubules. Type IV consisted of papillary calculi in which the core, which is situated near, but not in, the concave zone, is formed by intergrown COM crystals and organic matter. Many factors, including urinary alterations (eg, hyperoxaluria), associated diseases (eg, hypertension, diabetes), and consumption or exposure to cytotoxic substances (eg, analgesic abuse) were associated with these types of calculi. CONCLUSIONS: Our findings have indicated that injury is the first cause of papillary COM calculus formation, with the location of the injury determining the morphology of the resulting calculus.

Phytate inhibits bovine pericardium calcification in vitro.

OBJECTIVE: The present study examined the inhibitory effects of pyrophosphate, etidronate, and phytate on bovine pericardium calcification in vitro. METHODS: Bovine pericardium was glutaraldehyde fixed and then placed in a flow chamber in the presence of a synthetic physiological fluid alone (control) or the fluid plus various concentrations of pyrophosphate, etidronate, or phytate. Following a 96-h incubation, fragments were removed and assayed for calcification by measuring calcium and phosphorus levels. RESULTS: The data indicated that both pyrophosphate and etidronate at 1 mg/l (5.75 and 4.95 microM, respectively) inhibited bovine pericardium calcification, whereas neither agent had an effect at 0.5 mg/l (2.87 and 2.47 microM, respectively). Phytate was the most potent inhibitor of calcification, and the effects of this agent were apparent at levels as low as 0.25 mg/l (0.39 microM). CONCLUSIONS: While pyrophosphate, etidronate, and phytate were all able to inhibit bovine pericardium calcification in vitro, phytate was found to be the most effective.

Renal lithiasis and nutrition.

Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified through diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine) is discussed.

The role of glycoproteins in calcium oxalate crystal development.

OBJECTIVE: To assess the effects of a glycoprotein (mucine) on calcium oxalate crystal development in different conditions and situations, to clarify some of its possible effects. MATERIALS AND METHODS: Crystallization was assessed using a batch system in presence of mucine suspensions, by kinetic-turbidimetric measurements, and using a flow system in the presence of retained agglomerates of mucine, evaluating the precipitated calcium oxalate. RESULTS: In batch conditions low mucine concentrations (<15 mg/L) inhibited calcium oxalate nucleation and higher concentrations (<250 mg/L) inhibited calcium phosphate nucleation, whereas at high concentrations there was also promotion. The presence of an aggregate of mucine in the flow system provoked calcium oxalate monohydrate crystallization at 0.691 microg/h per mg of mucine. In flow conditions pyrophosphate at 11.5 micromol/L caused a decrease of 84% in the calcium oxalate crystallized on mucine, 1.32 mmol/L of citrate a decrease of a 83%, 20 mg/L of pentosan polysulphate a decrease by 80%, and 7.58 micromol/L phytate totally prevented the crystallization of calcium oxalate on mucine. CONCLUSION: All substances inhibiting calcium oxalate crystallization with the capacity to interact with calcium ions also have crystallization promoting properties when they are at sufficiently high concentrations, because of their capacity to form agglomerates or the insolubility of their calcium salts.

Simple classification of renal calculi closely related to their micromorphology and etiology.

BACKGROUND: Classification of renal calculi with clear correlation with the main urinary etiological conditions has been previously established. However, such information is complex and difficult to adapt to clinical routine practice. METHODS: A simple classification of renal calculi based on their structure and composition is proposed and applied to 2500 renal calculi to achieve the percentage of each category. The urines of 700 individuals chosen randomly have been analyzed and the results compared with those obtained with 51 healthy subjects. RESULTS: 12.9% calculi corresponded to calcium oxalate monohydrate papillary calculi, 16.4% to calcium oxalate monohydrate unattached calculi, 33.8% to calcium oxalate dihydrate calculi, 11.2% calcium oxalate dihydrate/hydroxyapatite mixed calculi, 7.1% hydroxyapatite calculi, 4.1% struvite calculi, 0.6% brushite calculi, 8.2% uric acid calculi, 2.6% calcium oxalate/uric acid mixed calculi, 1.1% cystine calculi and 1.9% various infrequent calculi. Based on the corresponding urinary analytical studies, each kind of calculus is related with the more frequently associated urinary alterations. CONCLUSIONS: An important aspect of this classification is the possibility to establish, by means of the correct study of the calculus, some of the main possible etiologic factors closely related to its formation.