Factor In Stone Formation Research Articles

THE EFFICACY OF DIETARY INTERVENTION ON URINARY RISK FACTORS FOR STONE FORMATION IN RECURRENT CALCIUM OXALATE STONE PATIENTS

Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.

Genetic Hypercalciuria

Hypercalciuria is an important, identifiable, and reversible risk factor in stone formation. The foremost and most fundamental step in dissecting the genetics of hypercalciuria is understanding its pathophysiology. Hypercalciuria is a complex trait. This article outlines the various factors that compromise the attempt to dissect the genetics of hypercalciuria, summarizes the clinical and experimental monogenic causes of hypercalciuria, and outlines the initial results from attempts in studying polygenic hypercalciuria. Finally, the problem is set in perspective of the current database, technologic advances and limitations are highlighted, and prospects of further advances in the field are speculated upon.

Renal stone disease, elevated iPTH level and normocalcemia.

There is a well established relationship between primary hyperparathyroidism and recurrent calcium-containing calculi. Traditionally, the diagnosis is confirmed by the presence of elevated intact parathyroid hormone (iPTH) and serum ionised calcium levels. The prevalence and role of elevated iPTH in the presence of normocalcemia in patients with renal stone disease is poorly understood. The aim of the present study was to describe the findings in patients who had renal stone disease, an elevated iPTH level and normocalcemia. During the last decade, 414 patients, who had normal renal function, were investigated and treated for renal calculi in the Renal Stone Clinic of the Toronto Western Hospital. Of these 414 patients, 40 (9.6%) had an elevated intact iPTH level and normal serum calcium (total and ionised) on repeated measurements. In all these patients we performed detailed clinical and laboratory investigations to determine risk factors for stone formation. Correlation analysis was done using Pearson test and the weights of factors influencing iPTH level were compared using multiple regression analysis. The average duration of a history of stone disease was 12.0 +/- 10.5 years. Most of these patients had passed their stones spontaneously, 15 underwent lithotripsy, in six the stones were removed by basket catheters and one patient each had partial nephrectomy, nepholithotomy or uretero-lithotomy. Twelve had a positive family history, two had history of intestinal malabsorption and one patients had a history of immobilisation. All of these patients had elevated serum parathyroid hormone in the range of 3% to 134% (median 20.5%) above upper limit of normal (F = M); all had normal serum total and ionised calcium and normal urine excretion of calcium (except in one). Additional risk factor for stone formation included: low level of 25-hydroxyvitamin D in four patients, low output and high urine osmolality in four patients, high urine sodium in nine and high oxalate excretion in eight patients. Citrate excretion was low in seven, magnesium excretion in six patients and tubular reabsorption of phosphate in 22 patients. Urine hydroxyprolin was increased in two and decreased in four patients. Combined abnormalities were found in 14 while 17 patients did not have any abnormality apart from elevated iPTH level. Multiple regression analysis did not suggest that any of the selected predictors had a significant influence on PTH release. 9.6% of patients with recurrent kidney stones had normocalcemia and elevated iPTH level in the presence of normal renal function. The study did not show any distinct pattern of abnormalities that would suggest a mechanism of stone disease in these patients. Further investigations are necessary to determine the significance of elevated iPTH in normocalcemic patients with renal stone disease and establish whether we should consider neck exploration for parathyroidectomy in these patients.

The effects of human urine on the adhesion of calcium oxalate crystal to Madin-Darby canine kidney cells.

To determine the effect of human urine on the adhesion of calcium oxalate monohydrate (COM) crystals to Madin-Darby canine kidney (MDCK) cells in a model system in vitro. MDCK cells were exposed to COM crystals in the presence of various human urine samples. COM crystals adhering on MDCK cells were quantified by measuring the calcium concentration using atomic absorption analysis. The inhibitory activities were estimated individually for various urine samples from healthy subjects and recurrent stone formers. Human urine inhibited the adhesion of COM crystals to MDCK cells, with some variations between individual samples. The most potent inhibition of crystal adhesion was expressed by the macromolecular fraction of the urine. Pretreatment of crystals with human urine before exposure to the cells significantly reduced crystal adhesion, suggesting that human urine altered the properties of the crystal surface but not the cell surface. Coating of the crystals by some component(s) of human urine might be an important physiological event in preventing adhesion or retention of crystals in the renal tubules. Although the mechanisms by which crystal adhesion is prevented are unknown, a low potential for inhibiting adhesion may be a risk factor in stone formation because it permits crystal adhesion and retention in the tubules.

Bladder calculi in the pediatric augmented bladder.

Bladder augmentation is now a commonly accepted treatment in children with neuropathic bladder and other bladder anomalies. Bladder calculi have been reported in a third to a half of pediatric patients after bladder augmentation. We identify the incidence of bladder calculi and risk factors for stone formation in a large series of pediatric patients after bladder augmentation. We reviewed the records of 286 patients who underwent bladder augmentation between 1978 and 1994, assessed the incidence of and risk factors for bladder calculi, and reviewed treatment methods. Bladder calculi developed in 29 of the 286 patients (10%) who underwent bladder augmentation. The type of bowel used for augmentation did not affect the rate of stone formation except stomach, which did not lead to stone formation in any case. Stones formed more commonly after bladder outlet resistance procedures and in patients with catheterizable abdominal wall stomas. Patients underwent open cystolithotomy or cystolitholapaxy with an overall 44% recurrence rate and no statistically significant difference between treatment methods. Bladder calculi are a known complication of bladder augmentation. An increased risk of stone formation is associated with bladder outlet resistance procedures and catheterizable abdominal wall stomas. Daily irrigations to clear mucus and crystals as well as complete emptying of the augmented bladder may have important roles in decreasing stone formation.

Stone Formation After Augmentation Cystoplasty: The Role of Intestinal Mucus

Purpose We evaluated the role of mucus in urine after bladder augmentation and hypothesize that mucus acts as a possible etiological factor in stone formation. Materials and Methods Mucus was collected via centrifugation from the 24-hour urine specimens of 8 stone forming and 10 nonstone forming patients who were randomly selected from our augmentation population. The mucus and stones were lyophilized, and then analyzed via scanning electron microscopy and energy dispersive x-ray spectrometry for calcium, phosphate, magnesium and sodium. The 24-hour urine collections were also analyzed to determine any metabolic differences between the 2 groups. Results Scanning electron microscopy and energy dispersive x-ray spectrometry spectra showed increased calcium, phosphate, and magnesium, and significantly higher (p <0.05) calcium-to-phosphate ratios in the mucus of stone versus nonstone forming patients. Of the 8 stones examined all had viscous fluid (mucus) centers rich in calcium, phosphate and magnesium. Calcium-to-phosphate ratios in the corresponding mucus recovered from stone centers were similarly high. Urinary citrate levels were low in both groups, and calcium, phosphate and magnesium were within normal ranges. Conclusions Mucus appears to have an important role in the genesis of bladder stones after augmentation, possibly acting as a nidus. Metabolic changes following augmentation were similar in stone and nonstone forming populations. Our data suggest that mucous calcium-to-phosphate ratios may be predictive of future stone formation. Furthermore, there may be a benefit in instituting more aggressive measures aimed at clearing mucus from the bladder.

Variability of the calcium ion activity with pH in stone-forming and non-stone-forming urine

In recurrent renal stone-formers (N = 20) and matched healthy adults (N = 20), the actual activity of ionized calcium (alpha Ca2+) and pH were determined in whole urine with an ion-selective electrode. No significant difference was found for the actual median activity of ionized calcium, however the actual median pH was significantly higher in stone-formers compared to healthy adults (pH = 5.57 vs. pH = 5.24; p < 0.005). The relationship between Ca2+ activity and pH was studied in each collected urine by titration with HCl/NaOH. In all urines the Ca2+ activity decreased with increasing pH in a typical bifasic manner. All curves showed a characteristic "breaking point" at a similar median pH in the stone-formers and in the healthy adults (pH = 6.81 vs. pH = 6.77) (NS). However the slope of the curves in the stone-formers and healthy adults changed from a median value of delta lg alpha Ca2+/delta pH of -0.139 and -0.173 (NS) respectively, to a highly significant difference of -1.326 and -1.053 (p < 0.0001) between the groups, indicating increased binding/precipitation of Ca2+ in stone-formers than in healthy adults supporting the theory of the lack of inhibitors in stone-formers. The strong relationship between the activity of ionized calcium and pH, combined with a higher actual pH and a higher decrease of ionized calcium with pH in stone-formers than in healthy adults, indicates hydrogen ion as a major factor in stone-formation. The close relationship between Ca2+ activity and pH indicates the need for simultaneous measurements of the pH in order to interpret data for the Ca2+ activity. In order to preserve a low urinary pH, where Ca2+ is predominantly in a free ionic state, our results suggest that treatment with acidifying salts could be a logical choice in order to prevent stone-formation.

The Effect of Diclofenac Sodium on Urinary Concentration of Calcium, Uric Acid and Glycosaminoglycans in Traumatic Paraplegics

Non-steroidal anti-inflammatory drugs (NSAID) have been shown to decrease calcium excretion in the experimental animal, in human volunteers and in calcium stone formers. Paraplegics tend to be hypercalciuric during the first 2 years after their injury and this is said to be a predisposing factor for stone formation in these patients. The effect of the NSAID diclofenac sodium was studied in 12 traumatic paraplegics who had sustained their injury 1 to 6 months previously; 24-h urine samples collected before and 2 weeks and 4 weeks after oral diclofenac sodium 50 mg tds were analysed for calcium, uric acid, glycosaminoglycans (GAGs) and volume. There were no significant changes in urinary volume, uric acid and GAGs excretion. However, urinary calcium concentration and 24-h calcium excretion decreased significantly following 2 weeks' and 4 weeks' treatment with diclofenac sodium.

The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis

A dose-related toxicity syndrome of renal, cerebral, and liver dysfunction; metabolic acidosis; and deposition of calcium oxalate crystals in tissues is reported in association with various apparently unrelated treatments for a wide range of diseases. The parenteral nutrient xylitol, the hyperosmolar agent glycerol, the polysorbate emulsifiers (e.g., in vitamin E preparations), the anesthetic methoxyflurane, and possibly the experimental hypoglycemic agent dichloroacetate all produce a toxicity syndrome very similar to that of ethylene glycol poisoning. In long-term, high-dose oral toxicity studies with rodents, these or similar agents also produce calcium oxalate bladder stones and bladder tumors. Studies with both unlabeled and labeled agents in humans and animals and in vitro experiments with purified enzymes, tissue homogenates, and isolated hepatocytes have provided both strong circumstantial and direct evidence for the existence of minor pathways of carbohydrate metabolism and of oxidative dealkylation and dehalogenation reactions in drug biotransformations that link these agents to endogenous oxalate production. Because urinary oxalate is now considered to be a critical factor in stone formation and because it is increasingly accepted that 80-90% of urinary oxalate is produced endogenously, it is now possible to formulate pathways that link oxalate production with dietary macronutrients. Therapeutic modifications of diet, in vivo hormonal milieu, and intracellular metabolic controls in relation to endogenous oxalate production may provide new forms of treatment for urolithiasis.

Therapy With The Knife: Is It Still Needed for Renal Stones?

Therapy With The Knife: Is It Still Needed for Renal Stones?

Homozygous cystinuria in New South Wales

Homozygous cystinuria was ascertained in 110 individuals (44 men) from 78 families because of symptoms in the propositi. The most common renal symptoms were calculi which occurred in 91% of the propositi and in 52% of affected family members. One-third of patients had urinary tract infections. There was a high rate of renal morbidity at an early age; 16 patients had undergone nephrectomy at a mean age of 25 years (range, 12-40 years). Two-thirds of subjects had type I cystinuria on family testing--the same ratio as that reported in a previous study of cases detected by newborn screening in the same population--which eliminates genetic type as a risk factor for stone formation. On the basis of all data, a 62% probability of stone formation by the age of 25 years in patients with cystinuria was estimated. The patients were shorter than Australian controls, and an association between gout and cystinuria was found in adult men.

Oxalate Metabolism and Renal Calculi

Changes in oxalate excretion (together with changes in urinary volume) constitute the most important factors in altering the probability of renal stone formation. However, investigations on oxalate metabolism have been sparse, perhaps because of the lack of an accurate method for measuring oxalate in biologic fluids. Available data clearly implicate increased urinary oxalate excretion as the etiological factor in stone formation in two groups of patients--those with primary hyperoxaluria and those with gastrointestinal malabsorption. Evidence for the existence of hyperoxaluria in the patient with the "garden" variety of calcium oxalate stones is less persuasive.

Über Biokristallisation und epitaxie: Prof. Dr. Dr. h.c. A. Neuhaus zum 70. Geburtstag gewidmet

Based on investigation of more than 500 human urinary stones, it is assumed that epitaxial nucleation of stone-components on a suitably structured substrate, i.e. collagen-fibre, is the primary factor in stone-formation. The relatively rare occurrence of stone illness is explained by a blocking of the active centres on the surfaces of the epitaxial host by colloids, which are contained in normal urine.

Radiological significance of primary enterolithiasis.

In 5 instances of primary enterolithiasis the finding of an opaque laminated calculus on the plain radiograph of the abdomen represented the diagnostic clue to the presence of either Meckel's diverticulum or stenosing disease of the small bowel. Chronic stasis occurring in a diverticulum or proximal to an area of chronic partial obstruction and a favorable chemical milieu appear to be the basic factors in stone formation in the intestine. Enteroliths are not rare and should be considered more frequently in the evaluation of an abdominal calcification when its nature is not immediately apparent.