Urine is a saturated equilibrium and not a metastable supersaturated solution: evidence from crystalluria and the general composition of calcium salt and uric acid calculi

A computer algorithm is described which allows urine to be modelled as a saturated equilibrium solution with respect to any combination of the solids calcium oxalate, calcium hydrogen phosphate (brushite), amorphous calcium phosphate, uric acid, sodium hydrogen urate and ammonium hydrogen urate. It is demonstrated that this model of urine, unlike the widely accepted metastable supersaturated solution model, explains the long-known calcium salt crystalluria versus pH curves of both non-stone-forming and stone-forming urine. Further, the saturation model accounts for why most “infection” stones do not contain calcium oxalate and why most “urate” stones are composed solely of uric acid and not admixed with alkali metal hydrogen urate salts. The supersaturation model of urine cannot explain satisfactorily these well-known phenomena. For example, the supersaturation model predicts that virtually all“infection” stones should contain calcium oxalate along with calcium phosphate and, perhaps, struvite. Received: 18 November 1998 / Accepted: 25 March 1999     

Clinical and biochemical profile of patients with “pure” uric acid nephrolithiasis compared with “pure” calcium oxalate stone formers

The purpose of the present study was to compare the clinical characteristics of “pure” uric acid (UA) stone formers with that of “pure” calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had “pure” UA stones and 29 had “pure” CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 ± 11.8 years vs. 44.5 ± 10.0 years; P = 0.003); they had higher mean weight (88.6 ± 12.5 kg vs. 78.0 ± 11.0 kg; P = 0.001) and body mass index (29.5 ± 4.2 kg/m² vs. 26.3 ± 3.5 kg/m²; P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with “pure” UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 ± 0.20 vs. 5.93 ± 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 ± 56.3 mg/24 h vs. 181.3 ± 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of “pure” UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.     

Calcium stone disease: a multiform reality

In calcium renal stones, calcium oxalate and calcium phosphate in various crystal forms and states of hydration can be identified. Calcium oxalate monohydrate (COM) or whewellite and calcium oxalate dihydrate (COD) or weddellite are the commonest constituents of calcium stones. Calcium oxalate stones may be pure or mixed, usually with calcium phosphate or sometimes with uric acid or ammonium urate. The aim of this study was to compare the clinical and urinary patterns of patients forming calcium stones of different composition according to infrared spectroscopic analysis in order to obtain an insight into their etiology. The stones of 84 consecutive calcium renal stone formers were examined by infrared spectroscopy. In each patient, a blood sample was drawn and analysed for serum biochemistry and a 24-h urine sample was collected and analysed for calcium, phosphate, oxalate, citrate and other electrolytes. We classified 49 patients as calcium oxalate monohydrate (COM) stone formers, 32 as calcium oxalate dihydrate (COD) stone formers and three as apatite stone formers according to the main component of their stones. Patients with COM stones were significantly older than patients with COD stones (P<0.002). Mean daily urinary calcium and urinary saturation with respect to calcium oxalate were significantly lower in patients with COM than in those with COD stones (P<0.000). Patients with calcium oxalate stones containing a urate component (10%) presented with higher saturation (P<0.012) with respect to uric acid in their urine (and lower with respect to calcium oxalate and calcium phosphate, respectively P<0.024 and P<0.003) in comparison with patients without a urate component in the stone. Patients with calcium oxalate stones with a calcium phosphate component (15%) showed higher (P<0.0016) urinary saturation levels with respect to calcium phosphate (and lower with respect to uric acid (P<0.009), compared with patients forming stones without calcium phosphate or with a low calcium phosphate component. Patients with calcium stones mixed with urate had a significantly lower urinary pH (P<0.002) and urinary calcium (P<0.000), and patients with calcium phosphate >15%, higher urinary pH (P<0.004) and urinary calcium (P<0.000). In conclusion, in the evaluation of the individual stone patient, an accurate analysis of the stone showing its exact composition and the eventual presence of minor components of the stone is mandatory in order to plan the correct prophylactic treatment. Patients with calcium stones could require various approaches dependent on the form and hydration of the calcium crystals in their stones, and on the presence of minor crystalline components that could have acted as epitaxial factors.     

Chinese herbal medicines and their efficacy in treating renal stones

In herbal treatment of kidney stones, anti-lithics are used to “dissolve” the stones or aid their passing to guard against further retention. Diuretic action is also needed to increase the amount of fluid going through the kidneys and flush out the deposits. Previous clinical studies have shown that herbal medicines and their concoctions could be used to inhibit calcium oxalate crystallization. However, the pharmacodynamics and in-vitro effects of such medicines have not been established. Five Chinese herbal medicines were selected based on their usefulness in treating stone disease. A 96-well plate oxalate-induced turbidity in artificial urine was used to evaluate the efficacies of the different herbal medicines on calcium oxalate crystallization. The metastable limit was determined and the nucleation rate was derived from 12-min time-course measurement of turbidity at 405 nm. Phase-contrast microscopy was used to visualize the crystals. The results showed that with increasing concentrations of herbal extracts, smaller calcium oxalate crystal sizes were observed. Overall, the five herbal medicinal extracts tested were able to promote nucleation of calcium oxalate crystals while at the same time decreasing the size. This in-vitro crystallization confirms that prophylaxis of renal stones could be achieved by reducing overall supersaturation through promotion of small crystal nucleates and concomitant pharmacological diuretic action of herbal medicines. Clinical studies will provide more definitive conclusions.     

The increased risk of urinary stone disease in betel quid chewers

The chewing of betel quid is a common practice in many countries of the world, particularly in Southeast Asia. The quid consists of a preparation of areca nut, betel leaf and calcium hydroxide “lime” paste (“chuna”). For the first time, we present a study that links its use to urinary stone disease. Eight patients (seven male and one female) who presented to our Stone Unit with recurrent urinary stones were included in the study. All were from the Indian subcontinent and were found to regularly chew betel. The patients underwent metabolic screening including blood, random urine and 24-h urine tests, quantitative chemical analysis of their calculi (where possible) and each completed a 7-day Diet Diary on his/her free, home diet. The study demonstrated a high incidence of hypercalciuria, a tendency to pass an alkaline urine and low urinary citrate excretion among the patients. Together these urinary risk factors increase the probability of developing both calcium phosphate-containing and calcium oxalate-containing stones. In support of this hypothesis, the patients were found to form stones consisting mainly of calcium phosphate but mixed with calcium oxalate. It is concluded that the use of calcium hydroxide “chuna” in the betel quid is the major contributor to the cause of urinary stones in its users. Moreover, the development of urinary lithiasis in such patients may be a precursor to milk-alkali syndrome in those individuals whose chewing habit is more extensive than in the patients in this study and who do not seek to decrease their habit over the long term.     

A nidus,crystalluria and aggregation: key ingredients for stone enlargement

The in vitro study of calcium oxalate (CaOx) stone formation is usually based on crystallisation models but it is recognised that both healthy individuals and stone formers have crystalluria. We have established a robust in vitro stone growth model based on the principle of mixed suspension, mixed product removal system (MSMPR). Utilising this technique we studied the influence of CaOx crystallisation kinetics and the variation of calcium and oxalate concentrations on CaOx stone growth in vitro. Six stones received standard concentration of Ca (6 mM) and Ox (1.2 mM) in the medium while another six received variable concentrations of both Ca and Ox at various intervals. Stone mass was plotted against the experiment duration (typically 5–7 weeks). The stone growth was dependent on sufficient input calcium and oxalate concentrations and once triggered, stone growth could not be maintained at reduced calcium and oxalate inputs. The stone growth rate was positively correlated to the number of crystals in suspension around the stone and to the crystal nucleation rate and negatively correlated to the crystal growth rates. This leads to the conclusion that aggregation of crystals from the surrounding suspension was the dominant mechanism for stone enlargement.     

Difference in urinary stone components between obese and non-obese patients

The prevalence and incidence of urinary stone disease have been reported to be associated with body weight and body mass index (BMI). The aim of the study was to determine the difference in stone components among different BMI groups in patients with urolithiasis. Between Dec 2005 and Jan 2008, 907 urinary calculi were collected and analyzed by infrared spectroscopy. Most of the stones had been passed spontaneously, and some were collected during surgical manipulations. The data on patients’ gender, age, BMI at diagnosis, and stone composition were collected. The patients were classified as normal weight (18.5≤ BMI <24), overweight (24≤ BMI <27), or obese (BMI ≥27). Of the 907 patients with urinary stone disease, 27.7% had normal weight, 33.5% were overweight, and 38.8% were obese. The prevalence of calcium oxalate stones in the normal weight, overweight, and obese groups were 23.1, 30.6, and 34.9%, respectively (P = 0.002), and the prevalence of uric acid stones in the different groups was 2.8, 7.2, and 7.7%, respectively (P = 0.002). The prevalence of calcium oxalate and uric acid stones, but not that of calcium phosphate stones, increased with body size. There was a significant correlation between BMI and uric acid stones in the overweight and obesity groups, with odds ratios of 3.28 and 4.35, respectively. The prevalence and incidence of urinary stone disease were found to be associated with BMI. The percentage of uric acid and calcium oxalate stones was higher in obese than in non-obese patients. There was no apparent difference in the prevalence of calcium phosphate stones between obese and non-obese patients.     

Effects of citrate on renal stone formation and osteopontin expression in a rat urolithiasis model

Previous studies have described the inhibitory effects of citrate on calcium oxalate crystallization in place of crystal growth, but the effects of citrate on matrix proteins of stones has not been studied in vivo. To examine the effect of citrate on the matrix, we investigated the effect of citrate on osteopontin (OPN) expression, which we had previously identified as an important stone matrix protein. Control rats were treated with saline while rats of the stone group were treated with ethylene glycol (EG) and vitamin D₃, and the citrate groups (low-dose and high-dose groups) were treated with a citrate reagent compound of sodium citrate and potassium citrate, in addition to EG and vitamin D₃. The rate of renal stone formation was lower in the citrate groups than in the stone group. This was associated with a low expression of OPN mRNA in citrate-treated rats relative to that in the stone group. Citrate was effective in preventing calcium oxalate stone formation and reduced OPN expression in rats. Our results suggest that citrate prevents renal stone formation by acting against not only the crystal aggregation and growth of calcium oxalate but also OPN expression. Received: 7 June 2000 / Accepted: 20 September 2000     

Triamterene and renal stone formation: The influence of triamterene and triamterene stones on calcium oxalate crystallization

Summary A constant composition method has been used to compare the effects of triamterene renal stone material, synthetic triamterene precipitates, and soluble triamterene on the nucleation and crystallization kinetics of calcium oxalate in aqueous solutionin vitro. Crystallization studies have been carried out with the concentrations of calcium and oxalate ions maintained constant by the potentiometrically controlled addition of concentrated reagent solutions containing these ions. Triamterene renal stones were found to be much less effective than synthetic triamterene towards promoting the nucleation and crystallization of calcium oxalate from supersaturated solution. Renal stones composed of triamterene and matrix did not significantly enhance the deposition of calcium oxalate compared to nonseeded controls. The triamterene stones were also found to be ineffective in promoting calcium oxalate crystallization compared to other precipitates thought to be involved in the etiology of stone disease such as calcium hydroxyapatite. For stones of mixed triamterene/calcium oxalate composition, the enhancement of the nucleation and crystallization of calcium oxalate was directly related to the calcium oxalate content of the stone seed material. The presence of soluble triamterene or its metabolites in solution did not influence the crystallization kinetics of pure calcium oxalate seed materials. The results of this study indicate that triamterene in stones does not significantly contribute to further stone development through the enhancement of calcium oxalate crystallization processes.     

Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones

BACKGROUND: Alkaline citrate is thought to be helpful in reducing recurrences of calcium oxalate stones. The evidence for this is incomplete, there have been few good trials, all with their own limitations, and not all reported any significant benefit. In vitro studies are usually cited to support the clinical studies but these too have their drawbacks, in particular they relate to crystals and microscopic aggregates and not to actual stone growth. Here we test citrate in vitro using a model of macroscopic calcium oxalate stone enlargement. METHODS: Twelve calcium oxalate stones were grown at a time in a stone farm. Six were grown with 2 mmol/L citrate and six with 6 mmol/L citrate. Three protocols were tested; artificial urine, artificial urine with urinary macromolecules (UMM) from male controls and artificial urine with UMM from male stone formers. The stones were grown continuously for at least 24 days. RESULTS: In all three experiments the higher citrate concentration significantly reduced the growth rate of stones by more than 50% (P < 0.001). There was a small decrease in ionised calcium in the stone growth media (P < 0.001) and significant (P < 0.001) but small increase in pH (about 0.07 pH units). The inclusion of UMM also brought about a decrease in stone growth, particularly at 2 mmol/L citrate. CONCLUSION: Citrate inhibited stone growth in this laboratory model. This was true both in defined media and with addition of UMM. This adds to evidence justifying the use of alkaline citrate in calcium oxalate nephrolithiasis.     

Morphology of crystals in calcium oxalate monohydrate kidney stones

Both scanning electron microscopy and atomic force microscopy (AFM) have shown that calcium oxalate monohydrate kidney stones are made up from arrangements of sub micron crystals. The purpose of this investigation was to determine the morphology of these crystals which was obscured by the presence of organic matrix in our earlier study. Sections of stones were treated to remove the protein component of the matrix and then imaged using AFM. Images obtained after proteolysis show that the crystals are in the form of plates stacked on (100) surfaces. These results were confirmed by scanning electron microscopy observations from selected regions of calcium oxalate kidney stone surfaces. The observed crystal sizes are consistent with both the known matrix mass fraction and crystallite growth in the passage through the collecting duct.     

Stone composition and metabolic status

This paper aims to study the correlation between biochemical risk factors of the stone former and the type of oxalate stone formed, namely calcium oxalate monohydrate (COM) and calcium oxalate dehydrate (COD). A retrospective study of 487 patients who had been attending the urinary stone clinic, Trivandrum during 1998–2007 was conducted. The stones retrieved from them were subjected to chemical analysis and FTIR spectrographic analysis. They were categorized into COM, COD, mixed COM+COD and others. Of 142 pure calcium oxalate stone patients, 87 were predominantly COM stone formers and 55 COD stone formers. Their metabolic status of 24 h urine and serum was assessed. The values of urine calcium, phosphorus, uric acid, magnesium, creatinine, oxalate, citric acid, sodium and potassium, serum values of calcium, phosphorus, uric acid, magnesium and creatinine and calculated values of creatinine clearance, tubular reabsorption of phosphate, calcium magnesium ratio and calcium oxalate ratio were recorded. Comparison was made between the COM stone group and the COD stone group. Patients forming COM stones had significantly higher mean values for urine calcium (P < 0.05), oxalate (P < 0.01) and magnesium (P < 0.05) levels and significantly lower level of urine calcium–oxalate ratio (P < 0.01) and urine calcium–magnesium ratio (P < 0.01) compared to COD stone forming patients. All other values failed to show significant difference. Patients, with higher urine oxalate, formed COM stones. Those with low magnesium (which is an inhibitor) formed more of COD stones. Urine calcium was high in both groups without showing significant variation from the mean. In patients with high calcium–oxalate and calcium–magnesium ratios, there is higher chance of forming a COD stone than COM. Identification of the crystallization pattern of the calcium stone will help in selecting treatment modalities.     

Presence of lipids in urinary stones: Results of preliminary studies

Summary The presence of lipids in urinary stones was determined by histochemical and biochemical methods. When crystals of calcium oxalate, made by mixing calcium chloride and potassium oxalate solutions and sections of human calcium oxalate urinary stones, were exposed to osmium vapors, there was no staining of the pure crystals whereas the stone sections were stained. De-paraffinized sections of demineralized calcium oxalate stones showed positive sudanophilia on staining with Sudan black B. Both these experiments indicate the presence of lipids in calcium oxalate stones. Lipids were extracted from uric acid, struvite, and calcium oxalate stones using standard techniques. Phospholipids were separated by one-dimensional thin layer chromatography. All the stones studied contained lipids. In calcium oxalate stones they accounted for 10.15% of the matrix. Calcium oxalate and struvite stones contained more phospholipids than uric acid stones. Cardiolipin, sphingomyelin, phosphatidyl choline, phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, and phosphatidyl glycerol were identified in lipid extracts. Demineralization by ethylenediaminetetraacetate (EDTA) treatment increased lipid output from calcium oxalate stones by 15.5%.     

A stone farm: development of a method for simultaneous production of multiple calcium oxalate stones in vitro

We have previously shown how individual calcium oxalate stones of about 1 cm can be grown in vitro. While this proved a design concept, it was severely limited as an experimental tool because of the time required to undertake comparative studies. Here we describe a development of this system in which six parallel pairs of stone generators are supplied with feed solutions generating a medium that is supersaturated with calcium oxalate. Twelve stones were grown simultaneously in aseptically prepared artificial urine over a period of 32 days from 100 mg to about 250 mg. Flow rates, pH and [Ca²⁺] were stable and reproducible over the course of the experiment. Sodium azide (0.02%) was included in the growth medium of six stones and caused a modest decrease in growth rate from 5.5 to 3.4 mg/day. The experimental design is such that this was readily detectable both visually and statistically (p<0.001). This multiple stone growing system (a stone farm) shows improved consistency and illustrates the statistical power of the technique. Azide has only a minor effect on the growth kinetics and can be used as an antibacterial agent in studies involving urinary macromolecules. The technique is suitable for practical and meaningful investigation of calcium oxalate stone formation in vitro.     

Plasma oxalate level in pediatric calcium stone formers with or without secondary hyperoxaluria

Plasma oxalate (POx) concentration is significantly elevated in primary hyperoxaluria, severe renal failure or ethylene glycol poisoning. In these conditions, the degree of hyperoxalemia correlates with the severity of systemic calcium oxalate (CaOx) deposition and should be therefore carefully monitored. Although secondary hyperoxaluria (secHyOx) is a common finding in pediatric patients with kidney stone disease, very little is known about POx in this condition. We therefore evaluated POx level in 59 children and adolescence with calcium urolithiasis (34 confirmed by CaOx stone analysis and 25 children with a strong clinical suspicion of this type of urolithiasis), with or without “mild” secHyOx. A control group consisted of 41 healthy sex- and age-matched children. We found that POx was significantly increased in children with calcium urolithiasis and secHyOx compared to healthy children (9.16 ± 3.60 vs. 6.42 ± 2.53 μmol/l), but that was not the case in children with calcium urolithiasis but with normal urinary oxalate excretion (7.12 ± 3.33 μmol/l). We conclude that POx may be slightly increased in some pediatric calcium stone formers with secHyOx, probably related to intestinal oxalate hyperabsorption.     

Calcium carbonate crystals promote calcium oxalate crystallization by heterogeneous or epitaxial nucleation: Possible involvement in the control of urinary lithogenesis

A large proportion of urinary stones have calcium oxalate (CaOx) as the major mineral phase. In these stones, CaOx is generally associated with minor amounts of other calcium salts. Several reports showing the presence of calcium carbonate (C_aCO₃) and calcium phosphate in renal stones suggested that crystals of those salts might be present in the early steps of stone formation. Such crystals might therefore promote CaOx crystallization from supersaturated urine by providing an appropriate substrate for heterogeneous nucleation. That possibility was investigated by seeding a metastable solution of⁴⁵Ca oxalate with vaterite or calcite crystallites. Accretion of CaOx was monitored by⁴⁵Ca incorporation. We showed that (1) seeds of vaterite (the hexagonal polymorph of C_aCO₃) and calcite (the rhomboedric form) could initiate calcium oxalate crystal growth; (2) in the presence of lithostathine, an inhibitor of C_aCO₃ crystal growth, such accretion was not observed. In addition, scanning electron microscopy demonstrated that growth occurred by epitaxy onto calcite seeds whereas no special orientation was observed onto vaterite. It was concluded that calcium carbonate crystals promote crystallization of calcium oxalate and that inhibitors controlling calcium carbonate crystal formation in Henle’s loop might play an important role in the prevention of calcium oxalate stone formation.     

Animal models of kidney stone formation: an analysis

Calcific kidney stones in both humans and mildly hyperoxaluric rats are located on renal papillary surfaces and consist of an organic matrix and crystals of calcium oxalate and/or calcium phosphate. The matrix is intimately associated with the crystals and contains substances that can promote as well as inhibit calcification. Osteopontin, Tamm-Horsfall protein, bikunin, and prothrombin fragment 1 have been identified in matrices of both human and rat stones. Hyperoxaluria can provoke calcium oxalate nephrolithiasis in both humans and rats. Kidney-stone-forming rats are hypomagnesuric and hypocitraturic during nephrolithiasis. Human stone formers may have the same disorders. Males of both species are prone to develop calcium oxalate nephrolithiasis, whereas females tend to form calcium phosphate stones. Oxalate metabolism is considered to be almost identical between rats and humans. Thus, there are many similarities between experimental nephrolithiasis induced in rats and human kidney-stone formation, and a rat model of calcium oxalate nephrolithiasis can be used to investigate the mechanisms involved in human kidney stone formation.     

Developmental morphology of calcium oxalate foreign body stones in rats

Summary Calcium oxalate bladder stones were induced in male rats by implanting plastic foreign bodies and by adding ethylene glycol to their drinking water. The foreign body surface was first coated with cellular debris and some amorphous material. Encrustation with crystals of calcium oxalate started on the third day of implantation. Within 2 weeks the entire surface of a foreign body was covered with crystals and some noncrystalline material. Calcium oxalate monohydrate crystals consisted of platelike crystallites arranged in hemispherulitic or spherulitic habit. Calcium oxalate dihydrate crystals were basically dipyramidal, a majority of them showing interpenetrant twinning. The stone grew by confluent crystal growth and crystal aggregation. A transformation of calcium oxalate monohydrate crystals to calcium oxalate dihydrate also occurred. The matrix consisting of cellular debris and urinary macromolecules was universally distributed in the stone including the inside of crystal bodies.     

Presence of lipids in urine,crystals and stones: implications for the formation of kidney stones

BACKGROUND: Cell membranes and their lipids play critical roles in calcification. Specific membrane phospholipids promote the formation of calcium phosphate and become a part of the organic matrix of growing calcification. We propose that membrane lipids also promote the formation of calcium oxalate (CaOx) and calcium phosphate (CaP) containing kidney stones, and become a part of their stone matrix. METHODS: Human urine, crystals of CaOx and CaP produced in the urine of healthy individuals, and urinary stones containing struvite, uric acid, CaOx and CaP crystals for the presence of membrane lipids were analyzed. Crystallization of CaOx monohydrate at Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidylglycerol (DOPG), palmitoyloleoylphosphatidylglycerol (POPG) and dimyristoylphosphatidylglycerol (DMPG) was investigated to directly demonstrate that phospholipid assemblies can catalyze CaOx nucleation. RESULTS: Urine as well as CaOx and CaP crystals made in the urine and various types of urinary stones investigated contained some lipids. Urine of both CaOx and uric acid stone formers contained significantly more cholesterol, cholesterol ester and triglycerides than urine of healthy subjects. However, urine of CaOx stone formers contained more acidic phospholipids. The organic matrix of calcific stones contained significantly more acidic and complexed phospholipids than uric acid and struvite stones. For each Langmuir monolayer precipitation was heterogeneous and selective with respect to the orientation and morphology of the CaOx crystals. Crystals were predominantly monohydrate, and most often grew singly with the calcium rich (10-1) face toward the monolayer. The number of crystals/mm2 decreased in the order DPPG> DPPC and was inversely proportional to surface pressure and mean molecular area/molecule. CONCLUSIONS: Stone forming conditions in the kidneys greatly impact their epithelial cells producing significant differences in the urinary lipids between healthy and stone forming individuals. Altered membrane lipids promote face selective nucleation and retention of calcium oxalate crystals, and in the process become a part of the growing crystals and stones.     

Endoscopic evidence of calculus attachment to Randall's plaque

PURPOSE: It has been proposed that calcium oxalate calculi begin as small stones attached to the renal papillae at sites of Randall's plaque. However, no study has investigated the prevalence of attached stones in calcium oxalate stone formers or the relationship between stone attachment site and Randall's plaque. In this study we used endoscopic examination of renal papillae in stone formers undergoing percutaneous nephrolithotomy to investigate both issues. MATERIALS AND METHODS: Idiopathic calcium oxalate stone formers undergoing PNL for stone removal were enrolled in this study. Multiple papillae were examined and images were recorded by digital video. The presence or absence of papillary plaque and attached stones was noted, as was the site of stone attachment. RESULTS: In 23 patients, 24 kidneys and 172 renal papillae were examined. All kidneys were found to have papillary plaque and 11 of the patients had attached stones. Most papillae (91%) contained plaque. CONCLUSIONS: The prevalence of attached stones in calcium oxalate stone formers (48%) is greater than that previously reported for the general population. Attachment appears to be on Randall's plaque. The high prevalence of attached stones and the appearance of the attachment site are consistent with a mechanism of calcium oxalate stone formation in which stones begin as plaque overgrowth.