Mechanism Of Stone Formation Research Articles

Miscellaneous Stone Types

Drug-induced calculi and other rare stone types, such as ammonium acid urate or protein matrix stones, represent only about 2% of all renal calculi. However, the chance to easily reverse stone formation risk by discontinuing the offending drug makes identification of these entities important for clinicians. Additionally, study of these rare stone types contributes to understanding the biochemistry of stone formation. Drug-induced calculi may be classified into two groups based on the mechanism of stone formation. The first group includes drugs that provoke calculi composed of principally the drug and its metabolites. These medications tend to be poorly soluble, highly excreted in urine, and required at high dosages for long durations of therapy. Historically, sulfonamides, triamterene, and the HIV protease inhibitor indinavir were leading causes of drug-induced calculi. Uses of novel agents within these drug classes or alternative therapies have reduced the incidence attributed to these drugs, although risk from newer, commonly used medications–notably ciprofloxacin, aminopenicillins, ceftriaxone, ephedrine, and guaifenesin– are increasingly being recognized. Microscopic analysis for crystalluria or infrared spectroscopy of collected stones aid in recognition of calculi composed primarily of a drug and its metabolites. Understanding of drug metabolism and pharmacokinetics, particularly related to effects of urine pH on drug solubility and excretion, provides a rational basis for both prevention and treatment recommendations. When possible, clinicians should avoid or exercise great caution when prescribing these medications to patients with a prior history of stones. The second group of drug-induced calculi includes drugs that cause stones due to their metabolic effects, primarily on calcium or purine metabolism. Because these calculi are identical in physical composition to the more common nephrolithiasis types, careful medication history and high clinical suspicion are required for diagnosis of these drug-induced “metabolic” calculi. Most drugs in this class are readily expected based on their effects on urinary calcium excretion such as calcium/Vitamin D supplements and loop diuretics. Carbonic anhydrase inhibitors, including the antiepileptics topiramate and zonisamide, are also included in this group. Ammonium acid urate stones are endemic in developing countries due to dietary limitations and recurrent diarrheal illness, but rarely occur in developed countries. Identification of these stones should raise clinical suspicion of epidemiologic risk factors including recurrent urinary tract infections with urea-splitting organisms, inflammatory bowel disease, and laxative abuse. Interestingly, these unusual clinical scenarios can recapitulate a common biochemical pathway to stone formation. Protein matrix stones are another unusual stone type associated with specific epidemiologic factors, namely recurrent urinary infections and proteinuric end-stage renal disease. Although distinctly rare, protein matrix stones provide opportunity to investigate basic biochemical mechanisms underlying stone formation.

Metabolic syndrome and bariatric surgery in stone disease etiology

To review the prevalence and mechanisms of stone formation in patients with metabolic syndrome and in those submitted to bariatric surgery. MetS is associated with urinary stone disease, which appears to be sustained by dietetic factors and insulin resistance. The latter represented in obesity and diabetes favors uric acid precipitation in urine via a more acidic urinary load. Patients submitted to modern bariatric surgery are at risk of nephrolithiasis and nephropathy as a consequence of malabsorption and hyperoxaluria, which are more consistent after Roux-en-Y gastric bypass than after gastric banding. Other stone risk factors such as hypocitraturia may also be present. Patients with metabolic syndrome and those submitted to modern bariatric surgery are both at risk of nephrolithiasis and nephropathy. Accurate stone screening careful monitoring of renal function and diet counseling are strongly encouraged in these patients.

In idiopathic calcium oxalate stone‐formers, unattached stones show evidence of having originated as attached stones on Randall’s plaque

To analyse the structure and composition of unattached stones in idiopathic calcium oxalate (CaOx) stone-formers (ICSF) and compare them to attached stones from the same cohort, to investigate whether there is more than one pathogenic mechanism for stone formation in ICSF. ICSF undergoing percutaneous nephrolithotomy or ureteroscopy for the treatment of nephrolithiasis gave consent to participate in this study. All accessible renal papillae were endoscopically imaged using a digital endoscope. All stones were removed and determined by the operating surgeon to be attached or unattached to the underlying papilla. Micro-computed tomography (micro-CT), which provides three-dimensional analysis of entire stones, was used to compare the structure and composition of attached and unattached stones. Of 115 stones collected from nine patients (12 renal units), only 25 stones were found not to be attached to renal papillae. Of these 25 stones, four were lost and 12 showed definite morphological evidence of having been attached to tissue, probably having been displaced from papillae during access. For the remaining nine stones, micro-CT analysis showed at least one internal region of calcium phosphate within each of these unattached CaOx stones, i.e. the internal structure of the unattached stones is consistent with their having originated attached to Randall's plaque, and then having become detached but retained in the kidney, with new layers of CaOx eventually covering the original attachment site. CONCLUSIONS; Micro-CT analysis supports the hypothesis that in ICSF, both attached and unattached stones occur as a result of a common pathogenic mechanism, i.e. in this type of stone former, CaOx stones, even those not showing morphology that betrays attachment, all originate attached to interstitial plaque on the renal papilla.

Nephrolithiasis: Treatment, causes, and prevention

Factors that promote stone formation include low daily urine volumes; saturation of the urine with calcium, oxalate, calcium phosphate, uric acid, or cystine; acidic urine; and bacterial infection. The author identifies the mechanisms of stone formation and outlines management aimed at preventing recurrences.

Pancreatic lithiasis and intraductal papillary‐mucinous neoplasm with special reference to the pathogenesis of lithiasis

In pancreatic lithiasis in elderly autopsy cases, the stones are small and the pancreatic duct is changed very slightly when viewed by simple X-ray film, pancreatic ductography and gross appearance. Histologically, a slight fibrous increase is seen very locally, but findings consistent with chronic pancreatitis are not found throughout the whole pancreas. However, marked, diffuse and irregular dilatation of the pancreatic duct is frequently found in operative cases with chronic pancreatitis and pancreatic stones. These findings show that the changes seen with aging and with chronic pancreatitis can be distinguished based on the findings of pancreatic ductography. Mucin production in epithelia in intraductal papillary-mucinous neoplasm (IPMN) may not be strongly associated with the pathogenesis of pancreatic lithiasis. Pancreatic lithiasis may be related to squamous cell metaplasia. IPMN and dilatation of the pancreatic duct are closely associated with mucin production. An increase in intraductal pressure of the pancreatic duct may be somewhat related to the mechanism of stone formation. The incidental co-existence of pancreatic epithelia with pancreatic lithiasis in patients with chronic pancreatitis and the development of IPMN may also be possible. IPMN and pancreatic lithiasis may be related through the mechanism(s) of their pathogenesis, their synergism and the pathogenesis of stone formation. The relation between mucinous metaplasia and stone formation is slight and, therefore, there may be only a weak correlation between IPMN and pancreatic stones. This may explain why there are few reports of the co-existence of IPMN and pancreatic stones (Kimura in Kan Tan Sui 58:485-492, 2009).

Interaction of a complexing agent with urolith as the basis for efficient little-invasive therapy of phosphaturia

The solubility of phosphate–oxalate urinary calculi in solutions of complexing agents was studied using a specially developed flow reactor at 37°C. The treat� ment of calculi 30–90 mg in weight for 2 h was found to significantly change the surface structure of the cal� culi and decrease the sample weight. The average sol� ubilities of uroliths in a solution of sodium citrate Na 3 Cit (5%, pH 8.6), a citrate buffer solution (pH 6.4), and a solution of sodium ethylenediaminetetraacetate Na 2 H 2 EDTA (pH 4.6) are 17.5 ± 4, 35.2 ± 3, and 54.2 ± 8 wt %, respectively. Based on the results obtained, developed litholysis methods of residual concrements are proposed. Urolithiasis is a widespread disorder all over the world, affecting no less than 5–10% of population. More than 70% of calculi are made of calcium oxalate and calcium phosphate or their mixtures [1–3]. In this connection, no wonder that a wide circle of researches are interested in understanding mecha� nisms of stone formation, inhibiting stone deposition, and determining the conditions for spontaneous dis� charge of concrements [3–7]. In particular, citrate and ethylenediaminetetraacetate anions were shown [6, 7] to be inhibitors of deposition due to formation of complexes with Ca 2+ ion [8]. Citrate ions excreted in urine are precisely the species, which play this role in organism [4, 5]. In the present work, we studied in vitro interaction of aqueous solutions of chelating agents with phos� phate–oxalate calculi in order to develop a quantita� tive experimental base for chelation therapy. EXPERIMENTAL Reagents Na2H2EDTA (more than 99%, Che� mapol) and Na 3 Cit (more than 99%, Panreac) were used without additional purification. The reagents were dried in vacuum at 80°C to constant weight. The weighed salt samples were dissolved in appropriate vol� umes of bidistilled water. A citrate buffer (pH 6.4) was prepared by a standard procedure [9]. Phosphate– oxalate stones were obtained after surgical procedures (pyelolithotomy or ureterolithotomy) at Ivanovo State

Childhood urinary stones induced by melamine-tainted formula: how much we know, how much we don't know

Through screening, diagnosing, and treating childhood urinary stones induced by melamine-tainted formula, Chinese doctors obtained more experience with the clinical as well as the imaging features of the stones, although there still are many questions regarding melamine-associated stones. By reviewing the earlier reports on animals along with our recent experiences with humans, we concluded that there was no evidence either from animal experiments or from humans to support the direct toxicity of melamine on the kidney, although a feasible follow-up and assessment might be needed. It is also speculated that further studies on the mechanism of stone formation may need to take into account human internal metabolism changes and tubular function.

A formal test of the hypothesis that idiopathic calcium oxalate stones grow on Randall’s plaque

To confirm that more than half of all idiopathic calcium oxalate (CaOx) stones grow on interstitial plaque, as CaOx stones can grow attached to interstitial apatite plaque but whether this is the usual mechanism of stone formation is uncertain. In nine idiopathic CaOx stone formers (ICSF) undergoing percutaneous nephrolithotomy or ureteroscopy all accessible renal papillae were endoscopically imaged using a digital endoscope. All stones were removed intact, and recorded by the operating surgeon as being attached or unattached; for all attached stones the surgeon determined if the site of attachment was to plaque. This determination was further verified by reviewing the intraoperative video record, and only instances where plaque was reliably seen on video were used for analysis. Surgical observations were further validated by a combination of microcomputed tomographic analysis and papillary biopsy. The results were analysed statistically using fixed-sample testing and group sequential sampling. The nine patients had a total of 115 stones, primarily CaOx; 90 stones were attached. Of these, 81 were attached to plaque; surgeons could not visualize the site of attachment with sufficient clarity to judge in the other nine cases. Based on these data, the final point estimate for the number of stones attached to plaque was 0.754 (95% confidence interval 0.575-0.933; P = 0.013). In ICSF most stones grow attached to papillae, on plaque, so growth on plaque is the main mechanism for stone formation in this very common group of patients.

Diagnosis and spectrum of melamine-related renal disease: Plausible mechanism of stone formation in humans

Background An epidemic of urinary stones affecting children after consumption of melamine tainted milk is unfolding. We defined clinicopathological features of the disease for diagnosis, monitoring, and treatment of this group of patients. Methods A clinicopathological study on exposed children with ultrasonographic evidence of urolithiasis was conducted. Melamine and cyanuric acid levels in the urine were determined by mass spectrometry. Results Disease severity varied from acute renal failure with hydronephrosis to symptomatic or asymptomatic stones with or without abnormal urinalysis. All cases were aged < 3 y with > 50% cases having predisposing urinary metabolic risk factors for urolithiasis. Most of the stones were located in the renal pelvis and measured 2.5–18 mm by ultrasonography. We found a strong correlation between renal stone size and urinary melamine concentration. For stones < 10 mm, a 10 μg/mmol creatinine increase in urinary melamine concentration is associated with approximately 1 mm increase in the size of the stone. The high degree of correlation strongly suggests that melamine is related to stone formation in humans. Using ROC analysis, we propose that patients who have a persistent melamine level above the optimal cut-off value of 7.1 μg melamine/mmol creatinine in urine might have a significant exposure of melamine-tainted products. Unlike melamine, urinary cyanuric acid is not significantly different between cases and controls. Pathophysiological findings from feeding animals with melamine and cyanuric acid may not be directly applicable to humans. Conclusion Both melamine and urine metabolic lithogenic factors are important for the formation of melamine-related stones. Apart from aiding with case screening and confirmation, the urine melamine level might as well be an indicator of residual melamine load in the body and thus is useful for following-up and monitoring of the confirmed cases. As the stones are small and can be passed out spontaneously, follow-up of these patients with urine melamine will be a convenient tool for monitoring the melamine load of the patients.

Renal Intratubular Crystals and Hyaluronan Staining Occur in Stone Formers with Bypass Surgery but not with Idiopathic Calcium Oxalate Stones

Whether idiopathic calcium oxalate (CaOx) stone formers form inner medullary collecting duct (IMCD) crystal deposits bears on pathogenetic mechanisms of stone formation. In prior work, using light and transmission electron microscopy, we have found no IMCD crystal deposits. Here, we searched serial sections of papillary biopsies from a prior study of 15 idiopathic calcium oxalate stone formers, 4 intestinal bypass patients with CaOx stones, and 4 non-stone-forming subjects, and biopsies from an additional hitherto unreported 15 idiopathic calcium oxalate stone formers and 1 bypass patient using polarized light oil immersion optics, for deposits overlooked in our original study. We found no IMCD deposits in any of 1,500 serial sections from the 30 idiopathic calcium oxalate stone formers, nor in 87 additional sections from a frozen idiopathic calcium oxalate stone former biopsy sample processed without exposure to aqueous solutions. Among 4 of the 5 bypass patients but in none of the 30 idiopathic calcium oxalate stone formers or 4 normal stone formers, we found tiny birefringent thin crystalline overlays on scattered IMCD cell membranes. We also found IMCD lumen deposits in two bypass patients that contained mixed birefringent and nonbirefringent crystals, presumably CaOx and apatite. In the bypass patients, we observed focal apical IMCD cell hyaluronan staining, which was absent in idiopathic calcium oxalate stone formers. The absence of any IMCD deposits in 1,500 serial sections of biopsies from 30 idiopathic calcium oxalate stone formers allows us to place the upper limit on the probability of their occurrence at approximately 0.002 and place the lower limit of their size at the resolution of the optics (<0.2 mu). The tiny deposits in bypass patients may be the initial crystal lesion.

Concentration effect of trace metals in Jordanian patients of urinary calculi

Due to the increase in the number of urinary calculi disease cases in Jordan, stone samples were collected from patients from various Jordanian hospitals (Princes Basma (PBH), King Abdullah University (KAUH), Al-Basheer (ABH) and Al-Mafraq (AMH)). This study concentrates on the effect of trace metals in patients of urinary calculi. Trace metals were detected in 110 urinary calculi samples using X-ray fluorescence (XRF) and atomic absorption spectroscopy (AAS) techniques. Of the calculi examined, 21 were pure calcium oxalate (CaOax), 29 were mixed calcium oxalate/uric acid, 23 were mixed calcium oxalate/phosphate (apatite), 25 were phosphate calculi (apatite/struvite), five were mixed calcium oxalate monohydrate/struvite, four were urate calculi (mixed ammonium acid urate/sodium acid urate) and three were pure cystine calculi. The concentration measurement of Ca and other trace metals levels has been found useful in understanding the mechanism of stone formation and in evaluating pathological factors. It has been found that Ca is the main constituent of the urinary calculi, especially those stones composed of calcium oxalate and calcium phosphate. The concentration of most of the trace metals that were analyzed was (Ca = 48.18, Na = 1.56, K = 0.9, Mg = 3.08, Fe = 1.17, Al = 0.49, Zn = 0.7, Cu = 0.19, Mn = 0.029, P = 10.35, S = 1.88, Sr = 0.306, Mo = 0.2, Cr = 0.146, Co = 0.05, Ni = 0.014)%. In conclusion, metals concentration in Jordanian patient's urinary calculi samples was higher than its equivalents of other patients'. It has been noted that there is no concentration of toxic trace elements (like Li, V, Pb, Cd, and As). Some heavy metals, however, were detected Mo, Cr, Co and Ni as traces. P and S ions are present in few calculi stones as traces.

Serum, urinary and stone zinc, iron, magnesium and copper levels in idiopathic calcium oxalate stone patients

Many theories have been put forward to explain the mechanism of stone formation and growth. The aim of this study was to investigate the urinary, serum and stone levels of zinc, iron, magnesium, and copper in patients with calcium oxalate stones and to investigate urinary and serum element levels in healthy controls and to find a possible connection between the elements and calcium oxalate stone formation. A total of 104 patients with calcium oxalate stones ranging in age from 3 to 79 years (mean 44.0 +/- 18.1) and 77 healthy controls ranging in age from 18 to 77 (mean 44.2 +/- 17.9) were included in this study. The mean urinary iron and copper levels in stone patients were significantly higher than healthy controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy controls were significantly higher than stone patients (P = 0.000). There was no significant difference in the serum levels of magnesium and copper in stone patients and healthy controls. Serum zinc and iron level were significantly high in healthy controls as compared to stone patients. Each stone had all 4 elements. Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu could be promotor of the calcium oxalate stone formation.

Calcium Oxalate Calculi Found Attached to the Renal Papilla: Preliminary Evidence for Early Mechanisms in Stone Formation

Calculi are commonly found attached to the renal papilla in calcium oxalate (CaOx) stone formers, but the mechanisms by which stones form in this manner are not well established. Data are presented from three attached stones collected from different patients. Stone morphology and composition were determined using micro computed tomography (CT) and infrared microspectrometry. One of the stones was composed of CaOx with a peripheral region of apatite, such as might have come from a Randall's plaque. Another stone was covered with large CaOx crystals but contained at least two layers of apatite, with no apatite regions exposed at the surface. The third stone contained CaOx with inclusions of apatite and more apatite on its surface, along with a substantial volume of poorly mineralized material that could not be identified. The complexity of these stones and their differing morphologies do not by themselves allow inference of the mechanism of stone formation. Future work will require the careful documentation of attached stones on the papilla, as well as study of the papilla after the stone has been removed, before it can be determined whether such diverse CaOx stones originate from the same or different underlying etiologies.

Biochemical and Stone-Risk Profiles With Topiramate Treatment

Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation. Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment. Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001). Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Urine protein markers distinguish stone-forming from non-stone-forming relatives of calcium stone formers

We have investigated urine protein inhibitors of calcium oxalate crystallization to determine whether variations in these proteins are associated with kidney stone disease and whether protein measurements improve the identification of stone formers compared with conventional risk factors (RF). Using Western blotting, we studied variations in the electrophoretic mobility patterns and relative abundances of crystallization-inhibitory proteins in urine from 50 stone-forming (SF) and 50 non-stone-forming (NS) first-degree relatives of calcium SF patients, matched by gender and age. Standard urine chemistry stone risk measurements were also made. Multivariate discriminant analysis was used to test the association of these proteins with nephrolithiasis. Differences in form and abundance of several urine proteins including inter-alpha-trypsin inhibitor (ITI), prothrombin fragment 1 (PF1), CD59, and calgranulin B (calB) were found to be associated with stone formation. By multivariate discriminant analysis, measurements of forms of PF1, ITI, and calB in men and ITI and CD59 in women, classified 84% of men and 76% of women correctly by stone status. In contrast, standard urine chemistry RF identified only 70% of men correctly and failed to distinguish female SF from NS. Thus a small subset of protein measurements distinguished SF from NS far better than conventional RF in a population of relatives of calcium SF, illustrating the significant association of these proteins with stone disease. Variations in these proteins may serve as markers of stone disease activity or vulnerability to recurrence and may provide new insights into mechanisms of stone formation.

Proteolysis and partial dissolution of calcium oxalate: a comparative, morphological study of urinary crystals from black and white subjects

Crystal adherence to the renal epithelium is widely regarded as a probable mechanism of stone formation. Intracrystalline proteins may provide access to the core of urinary crystals and thereby facilitate the dismantling of these crystals after their attachment to and phagocytosis by renal epithelial cells. The present study investigated the role of proteolysis and limited dissolution of urinary calcium oxalate (CaOx) crystals in South Africa's white and black populations with a view to understanding the remarkably low stone incidence in the black population compared with the whites. CaOx crystals were precipitated from filtered urine or ultrafiltered urine dosed with an intracrystalline protein, urinary prothrombin fragment 1 (UPTF1), isolated from white and black subjects. The crystals were fractured and subjected to proteolysis and/or limited dissolution before examination using field emission scanning electron microscopy (FESEM). FESEM data showed that CaOx crystals from white and black subjects were eroded by treatment with proteases. Cathepsin D caused the most significant crystal erosion, and more noticeable degradation of CaOx monohydrate (COM) crystals compared to CaOx dihydrate (COD). Limited dissolution studies showed the unique ultrastructures and fragmentation processes of COM and COD crystals. COM crystals appeared to be more susceptible to degradation and dissolution than CODs. Since COMs are predominant in blacks, compared with COD crystals from whites, it is speculated that the lower stone rate amongst South African blacks might be attributed partly to their more efficient destruction of retained COM crystals.

Endoscopic Renal Papillary Biopsies: A Tissue Retrieval Technique for Histological Studies in Patients With Nephrolithiasis

The mechanisms behind calcium nephrolithiasis remain unclear. Previous research has relied on animal models or cell lines, yielding limited insight into the pathophysiology of human calcium stone disease. To determine changes occurring in the human kidney during active stone disease we used an endoscopic renal papillary biopsy protocol in calcium stone formers undergoing percutaneous nephrolithotomy. Following stone burden clearance via percutaneous nephrolithotomy 15 idiopathic calcium oxalate and 4 ileal bypass stone formers underwent flexible and rigid nephroscopy. Biopsies from select papillae in the peripheral and interpolar regions were obtained with 5Fr flexible cup biopsy forceps. A papilla adjacent to the accessed calix was biopsied with 10Fr cup biopsy forceps. Cortical biopsies along the access tract were also obtained with the 10Fr forceps. All patients had successful biopsy completion. No complications were attributable to the biopsy process and no blood transfusions were required. Of the 19 patients 12 were contacted for followup at a mean of 21.7 +/- 9.0 months with none experiencing adverse sequelae such as bleeding or significant pain. A total of 14 patients had followup serum creatinine available showing that the difference in mean preoperative and postoperative values was not clinically significant (1.00 +/- 0.27 and 1.11 +/- 0.27 mg/dl, respectively). The quality of biopsied tissue permitted accurate immunohistochemical staining of crystal deposits and mineral analysis. Endoscopic papillary biopsies were performed safely in a small patient population. Tissue obtained using this protocol can be used for detailed histological and analytical studies, which may lead to significant advances in our understanding of stone formation mechanisms.

The Urinary Response to an Oral Oxalate Load in Recurrent Calcium Stone Formers

Dietary oxalate may contribute up to 50% to 80% of the oxalate excreted in urine. We studied the urinary response to an oral oxalate load in male and female idiopathic recurrent calcium oxalate stone formers with and without mild hyperoxaluria to evaluate the potential pathophysiological significance of dietary oxalate. A total of 60 recurrent calcium stone formers underwent an oral oxalate load test. Urine samples were obtained after an overnight fast. Each patient then received an oral oxalate load (5 mM. sodium oxalate dissolved in 250 ml. distilled water) and 3, 2-hour urine samples were obtained 2, 4 and 6 hours after the oxalate load. We compared the response to the oxalate load in patients with and without mild hyperoxaluria, and in male and female patients without hyperoxaluria. The peak urinary response occurred 4 hours after the oral oxalate load in all patients. Those with mild hyperoxaluria had a mean fasting urinary oxalate-to-creatinine ratio +/- SE of 0.027 +/- 0.003 and a mean peak urinary oxalate-to-creatinine ratio of 0.071 +/- 0.006. In comparison, patients with normal oxalate excretion had a fasting and peak urinary oxalate-to-creatinine ratio of 0.018 +/- 0.001 and 0.056 +/- 0.004, respectively (p <0.05). The mean 6-hour increment for urinary oxalate excretion after the oxalate load for patients with hyperoxaluria versus those with normal urinary oxalate excretion was 17.2 +/- 1.9 versus 12.1 +/- 0.98 mg. (p <0.05). In the subset of patients with normal urinary oxalate excretion mean 6-hour cumulative urinary oxalate excretion was 16.8 +/- 1.3 and 13.3 +/- 1.4 mg. in males and females, respectively (p not significant). Recurrent calcium stone formers with mild hyperoxaluria have higher fasting urinary oxalate and an exaggerated urinary response to an oral oxalate load compared with recurrent calcium stone formers with normal urinary oxalate excretion. Men and women stone formers without hyperoxaluria excrete similar fractions of an oral oxalate load. Increased gastrointestinal absorption and renal excretion of dietary oxalate may be a significant pathophysiological mechanism of stone formation in patients with mild hyperoxaluria.

SIALOLITHIASIS

Sialolithiasis is one of the most common problems that afflict the salivary glands and is a major cause of salivary gland dysfunction. Sialolithiasis is frequently encountered in clinical practice. The mechanism for stone formation is incompletely understood. The clinical diagnosis and standard management of sialolithiasis are discussed, and new modalities for treatment are also presented in this article.

In VitroModels for Studying Renal Stone Formation: A Clear Alternative

This paper discusses the limitations of using laboratory animals for direct in vivo observation of the development of renal stones. In fact, the majority of hypotheses related to mechanisms of stone formation have been based on the results of in vitro experiments. The relevance of in vitro experiments that allow the study of urolithiasis depends upon the degree of correspondence between the experimental conditions and those prevailing in the stone-forming kidney in vivo. For this reason, several in vitro experimental systems that attempt to reproduce the conditions found in vivo have been developed in order to study renal stone formation, which have been classified into two main groups: a) models to study papillary stone formation; and b) models to study "sedimentary" stone formation. These models are briefly described in this paper, and the information obtained was compared with that resulting from a study of the fine structure of real human renal calculi, in order to prove the validity of the models. It was concluded that the experimental in vitro models can closely reproduce the renal conditions under which human calculi are developed. This allows important data to be obtained about the aetiology of renal lithiasis, which is of great relevance to the development of effective treatments for this disease. Therefore, experimental in vitro models constitute a clear alternative to the use of laboratory animals.