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Purpose: Kidney stone disease is characterized by a relatively high rate of recurrence. In our study we analyzed the association between relative supersaturation and the risk of stone recurrence. Additionally, we examined the association between the risk of recurrence and changes in relative supersaturation and urinary composition after 1 week of medical treatment., Materials and Methods: We performed a post hoc analysis of data from a previously published randomized controlled trial comparing the effect of 2 diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Baseline and followup 24-hour urine parameters were used to calculate the relative supersaturation of calcium oxalate, calcium phosphate and uric acid using the EQUIL2, JESS and LithoRisk computer programs. Cox models were used to calculate the estimated association between each baseline relative supersaturation, and 1-week changes and the risk of recurrence during followup., Results: During a 5-year followup 35 patients (34%) experienced recurrence. A reduction in calcium oxalate relative supersaturation at 1 week was significantly associated with a lower risk of recurrence using the EQUIL2 calculation (for every 10% reduction from baseline HR 0.92, 95% CI 0.86-1.00, p = 0.044). However, there was no association for relative supersaturation calculated by other methods or for the relative supersaturation of other salts. Changes in the 24-hour urine excretion of citrate, potassium and magnesium were significantly associated with a risk of recurrence., Conclusions: In recurrent stone formers with hypercalciuria baseline values and changes in the relative supersaturation of calcium oxalate may be associated with the risk of recurrence. Changes in urinary citrate, potassium and magnesium following dietary intervention may also be predictive., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Intermittent fasting and curtailing water intake for extended periods were likely common in Paleolithic times. Today it occurs for religious and dietary reasons. This restriction in intake should cause a decrease in the urine flow rate while raising the concentration of certain substances in urine to the point of precipitation. In this study we measured the risk of CaHPO 4 precipitation following 18 hours of food and water deprivation., Materials and Methods: Urine samples were periodically collected from 15 healthy subjects who fasted and abstained from drinking any liquid for 18 hours. The urine constituents Ca 2+ , HPO 4 2- and pH involved in CaHPO 4 formation were measured at various times throughout the fasting day. A comparison was made with control data, which consisted of diurnal urine collections taken throughout a separate nonfasting day prior to the fasting day., Results: The mean ± SEM urine flow rate decreased significantly from 0.93 ± 0.1 ml per minute in the control group to 0.37 ± 0.05 ml per minute in the fasting group (p <0.05). Mean Na + and Ca 2+ excretion rates decreased significantly from 127 ± 12 to 54 ± 13 μmol per minute and from 3.2 ± 0.4 to 0.80 ± 0.21, respectively. Mean urinary Na + and Ca 2+ concentrations also decreased from 161 ± 11.6 to 122 ± 16.0 mmol/l and from 3.7 ± 0.5 to 2.0 ± 0.55, respectively. Urinary pH and the concentration of phosphate, citrate and magnesium were not significantly affected., Conclusions: Although the steady decrease in the urine flow rate was statistically significant during 18 hours of food and water deprivation, there was no evidence that the calculated risk of CaHPO 4 precipitation in the healthy subjects had increased., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Intestinal malabsorption can cause urinary stone disease via enteric hyperoxaluria. It has been shown that celiac disease, a common malabsorption disorder, is associated with an increased risk of calcium oxalate kidney stones in adults. Since no published data are available in the pediatric population, we analyzed urinary excretion of electrolytes in children with celiac disease to assess the risk of nephrolithiasis., Materials and Methods: The study population consisted of 115 children 1 to 16 years old (mean 5 years) with positive serological tests for celiac disease (anti-endomysium and anti-tissue transglutaminase antibodies) referred to us for jejunal biopsy to confirm the diagnosis. Assessment was requested because patients presented with poor growth, anemia, gastrointestinal disorders or a family history of celiac disease. After obtaining informed consent we performed urine tests to measure urinary variables and blood tests to exclude metabolic disorders and evaluate renal function., Results: All patients had a biopsy confirmed diagnosis of celiac disease. Oxaluria was normal in all children studied. However, levels of urinary calcium were decreased in patients with celiac disease and were inversely associated with disease severity (p = 0.0004)., Conclusions: In contrast to adults, increased urinary excretion of oxalate was not detectable in children presenting with celiac disease. Therefore, the risk of nephrolithiasis appears not to be increased compared to healthy children. The observed hypocalciuria probably further decreases the tendency to form kidney stones., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Cystic fibrosis is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentrations. Patients with cystic fibrosis also have an increased incidence of nephrolithiasis. We compared the results of metabolic evaluation in patients with cystic fibrosis with and without nephrolithiasis., Materials and Methods: A total of 496 patients were evaluated at our center, including 98 with a mean age of 25 years who had cystic fibrosis and complete metabolic evaluation available between 1996 and 2000. Of these patients 13 (13%) had a history of nephrolithiasis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation, including serum electrolyte measurement and 24-hour urine collection. Statistical analysis was done to compare the stone versus nonstone groups., Results: The incidence of nephrolithiasis in our study was 3%. We identified 13 patients 16 to 41 years old (mean age 27) with nephrolithiasis, of whom 62% had had multiple episodes. Flank pain was the presenting symptom in 9 of the 13 cases (69%). Renal ultrasound and computerized tomography were the most common imaging modalities. In 9 cases stones were passed without intervention, extracorporeal shock wave lithotripsy was required in 2 and ureteroscopy with stone extraction was done in 2. Calcium oxalate was the dominant stone composition in the 9 patients in whom stone analysis was performed. Metabolic evaluation of the stone versus no stone groups showed elevated urinary oxalate (45.5 versus 42.5 mg./24 hours), relative calcium oxalate supersaturation (5.3 versus 7.2) and decreased urinary citrate in the 2 groups. There was a statistical difference in citrate excretion with lower levels in stone formers (102 versus 218 mg./24 hours, p = 0.0007)., Conclusions: Patients with cystic fibrosis have an increased incidence of nephrolithiasis and are at high risk for recurrence. Metabolic evaluation is indicated in all patients with cystic fibrosis and urolithiasis since most have hyperoxaluria, urinary calcium oxalate supersaturation and decreased urinary citrate. Correcting detected stone risk factors in these cases may decrease stone recurrence.

We investigated the effect of urinary intestinal diversion on risk factors for calcium urolithiasis, such as calcium, phosphate, magnesium, uric acid, oxalate and citrate, in 3 groups of patients (Kock pouch, Indiana pouch and ileal conduit). Mean urinary volume was not significantly different among the 3 groups. Mean serum creatinine and 24-hour creatinine clearance in the continent reservoir group were better than in the ileal conduit group. Mean urinary excretion of calcium, phosphate and magnesium was significantly greater in the continent reservoir group than in the ileal conduit group. Although calcium excretion had a positive correlation with 24-hour creatinine clearance, calcium excretion per ml. per minute creatinine clearance still showed a significant difference. Increased calcium excretion is considered to reflect metabolic disturbances resulting from reabsorption of urinary solutes through the intestinal segments. Overall, there was no significant difference in the urinary parameters between the Kock and Indiana pouch groups. While mean urinary oxalate and citrate were within the normal range in all 3 groups, more than a third of the patients in each group were hypocitraturic (less than 100 mg. per day). In none of the 3 groups did the levels of urinary calcium, phosphate and magnesium, as well as other urinary risk parameters show any correlation with the duration of diversion. In summary, our study indicated that the continent urinary reservoir causes a long-term increase in urinary excretion of calcium, phosphate and magnesium. These urinary metabolic alterations might promote the formation of calcium urolithiasis as well as infectious stones. The degree of metabolic alterations may be greater with a continent reservoir than with an ileal conduit.

We investigated the occasional inaccuracy in the biochemical measurement of urine by comparing the values from untreated samples to those obtained following our experimental pre-treatment regimen, which prevents precipitation and dissolves visible crystals. Discrepancies were observed between some of the paired samples, especially with regard to calcium and uric acid (urate) concentrations. Moreover, considerable differences were recognized in fresh as well as stored urine specimens. Our findings demonstrate the need to develop accurate methods of processing urine for biochemical analysis with multichannel autoanalyzers.

Eighty patients with proved calcium urolithiasis participated in an outpatient study designed to define the most likely metabolic problem related to the cause of the stone disease. Diagnostic categories included absorptive hypercalciuria (33 patients), renal leak hypercalciuria (20 patients), hypomagnesiumuria (27 patients), hyperuricemia and hyperuricuria (16 patients), hyperoxaluria (15 patients), normal stone-former (4 patients), renal tubular acidosis (2 patients) and suspicion of hyperparathyroidism (7 patients). Of the 80 patients 40 had more than 1 defect. Patients with a high suspicion of hyperparathyroidism were excluded from the study. Based on these criteria treatment plans incorporating medications, diet or both were instituted. Of 21 patients observed for greater than 2 years 90 per cent have shown no new stone disease.

The management of 78 children with upper urinary calculi is described. Boys outnumbered girls by a ratio of 2 to 1. Two-thirds of the patients had identifiable metabolic causes, while the remaining third had infected renal lithiasis. In this latter group, all patients had had multiple urologic procedures, urinary infection, and stasis with diversionary and indwelling drainage devices. Contrary to earlier views, idiopathic renal lithiasis with or without hypercalciuria was the most common metabolic form of nephrolithiasis in children. Sixty-seven patients (86 per cent) were followed for an average of 7 1/2 years. With appropriate therapy, stone disease became inactive in 70 per cent of the children. The remaining 30 per cent continued with active disease--5 died of renal failure and 1 has received a renal allograft. Stone formation may be regarded as a solitary complication or one of several manifestations of a large number of underlying disorders. Along with a thorough search for etiologic factors there must be an equally aggressive therapeutic effort. Because the disease is ofter sporadic, careful long-term followup of the patients with active as well as those with inactive stone disease is mandatory.

To study whether human urine contains inhibitors against urease-induced crystallization, Jackbean urease and human urine, in amounts small enough (0.5 to 10 per cent) not to influence the ion concentration, buffering capacity or pH, were added to synthetic urine. The ammonia production and alkalinization that followed were independent of the amounts of human urine added. The addition of human urine gave a dose-related decrease in the amount of calcium phosphate and struvite precipitated on glass rods immersed in the synthetic urine, however. Addition of only 0.5 per cent human urine gave a reproducible decrease and when 10 per cent human urine was added to the synthetic urine the precipitation of calcium phosphate was reduced by 50 per cent and that of struvite by 75 per cent. The results thus indicate that human urine contains components with the ability to reduce the urease-induced crystallization.

Extracorporeal shock wave lithotripsy (ESWL) can require more than two thousand acoustic shocks to achieve an adequate degree of renal calculus comminution. A decrease in the number of shocks necessary for effective treatment offers both technical and clinical benefits. The results presented here demonstrate that it is possible in particular cases to increase substantially the degree of comminution produced using a fixed number of acoustic impulses by exposing the stones to solutions of controlled pH and chemical composition during acoustic shock treatment. The largest increase in comminution was observed for magnesium ammonium phosphate hexahydrate/apatite stones exposed to citrate solutions. The smaller particle sizes are shown to result not only from stone dissolution but also from an increase in the ease of stone fracture during acoustic shocking. The degree of comminution of the largest fragment sizes was also found to be slightly increased for calcium oxalate stones by exposure to synthetic urine of elevated pH. These chemical methods of increased stone comminution appear to be directly applicable to particular cases and may have general clinical utility if suitable conditions affecting all stones can be found.

The effect of oral administration of magnesium oxide on the crystallization in urine of calcium oxalate and brushite was determined in 4 cases of recurrent calcium nephrolithiasis. Each patient was evaluated while on a constant metabolic diet before, during and after therapy with magnesium (1,000 mg. magnesium as magnesium oxide per day). During magnesium therapy urinary hydrogen ion concentration increased by approximately 0.5 unit in all 4 patients and urinary calcium increased about 50 mg. per day in 2. Urinary oxalate decreased significantly in 1 patient and urinary phosphorus was reduced in 2. The urinary activity product ratio of brushite (state of saturation) increased, owing largely to the rise in urinary hydrogen ion concentration but that of calcium oxalate was not changed significantly by magnesium treatment. Although urinary magnesium increased significantly there was no significant change in the urinary formation product ratio (limit of metastability) or the rate of crystal growth of brushite or calcium oxalate. Thus, no beneficial effect of magnesium therapy could be demonstrated in this short-term study.

Urinary excretion of the most widely studied renal stone promoting (calcium, oxalate, uric acid and phosphate) and inhibiting (citrate, magnesium, pyrophosphate and glycosaminoglycans) factors, as well as the Tamm-Horsfall mucoprotein, was evaluated in 14 children with idiopathic calcium nephrolithiasis, 6 children with renal stone disease secondary to excretory malformations and 19 normal controls. No statistically significant differences in urinary excretion of promoting and inhibiting factors were found in children with idiopathic calcium nephrolithiasis but the relationship between promoting and inhibiting factors was changed as shown by an abnormal ratio of oxalate/citrate X glycosaminoglycans. This finding suggests that there is an imbalance between promoting and inhibiting factors in children with idiopathic calcium nephrolithiasis, and it is not detected by assay of each single substance.

We determined the bacteriology of apparently infected renal calculi and accompanying urinary tract infections, and assessed the potential clinical value of the culture results. Twenty-two branched renal calculi from 16 patients were cultured. Fifteen calculi were infected with 1 or more urease-producing gram-negative enteric bacterium, 2 were infected with a urease-producing bacterium and a nonurease-producing organism, and 5 were sterile. Immersion of infected stones in antimicrobial solutions before culture reduced or eliminated surface bacteria but usually did not eradicate bacteria within the stone. The bacteriology of a stone or stones could be predicted on the basis of available urine culture results in only 2 of the 16 cases. These data suggest that branched renal calculi associated with bacteriuria usually are infected but that documentation of infection and identification of the infecting organism require culture of the stone.

The 24-hour urinary excretion of various electrolytes, as well as the glomerular filtration rate, renal plasma flow and maximal rate of tubular excretion of para-aminohippuric acid was measured in each kidney of 10 patients with idiopathic renal lithiasis. Results in hypercalciuric patients indicate that, in contrast to earlier views, actively stone-forming, normally functioning kidneys are normocalciuric but hypophosphaturic in comparison to their mates with inactive or no stone disease, which are hypercalciuric but normophosphaturic. Therefore, hypophosphaturia rather than hypercalciuria may be an important calculogenic factor in some patients.

Sodium cellulose phosphate was given to 35 patients for recurrent formation of calcium-containing stones. During therapy urinary calcium decreased by 40% in the first month and remained at this lower level. In addition, urinary magnesium excretion was reduced and the urinary magnesium/calcium ratio remained unaffected. In these patients, who mostly had had calcium oxalate stones, the prophylactic effects of sodium cellulose phosphate was poor, with a 47% recurrence rate after 2 years. This lack of prevention, despite the significant reduction of the urinary calcium, is assumed to be owing to the effects of treatment on magnesium and oxalate metabolism. Side effects were common, mainly consisting of moderate gastrointestinal discomfort, and caused withdrawal of treatment in 8 patients. This fact contributes further to our opinion that sodium cellulose phosphate is not the drug of choice in cases of calcium oxalate stone formation.

Urine of male Sprague-Dawley rats was supersaturated for struvite and often contained struvite crystals. Ethylene glycol administration to these rats resulted in elevation of urinary oxalate and calcium oxalate supersaturation, and induced calcium oxalate crystalluria. Implantation of foreign bodies in their urinary bladders and changing their urinary ambient conditions by administering ethylene glycol for two weeks at two week intervals resulted in the formation of urinary stones of mixed composition containing calcium oxalate and struvite. Crystal-onto-crystal epitaxy did not appear to play any role in the development of these stones.

To evaluate renal function in kidney units exposed to vesicoureteral reflux we quantified the fractional renal excretion of magnesium and the maximal renal concentrating capacity in 22 renal units of infants and children who presented with grade III to V vesicoureteral reflux on standard voiding cystourethrography. The lowest normal value for maximal concentrating capacity and the highest normal value for fractional excretion of magnesium were set at 800 mOsm. per kg. and 8 per cent, respectively. Concentrating capacity was abnormal in all 22 renal units and the excretion of magnesium was abnormal in 5. Failure of a renal unit to retain magnesium normally was always associated with an inability to concentrate urine. We conclude that in cases of vesicoureteral reflux function of the distal part of the nephron is the first to become abnormal and concentrating capacity is a more sensitive indication of dysfunction than fractional excretion of magnesium.

Salmonella enteriditis has been previously found to have both unique inhibiting and augmenting properties on urinary stone formation. A series of in vitro experiments were performed in order to determine if the in vivo results could be explained in an in vitro model. Urinary phosphorus was measured before and after incubation with various bacteria, and was found to increase significantly when incubated with S. enteriditis (p less than 0.05). Urinary citrate was measured in a similar fashion following incubation with S. enteriditis and E. coli. A statistically significant decrease in urinary citrate was found in urine incubated with S. enteriditis (p less than 0.005). Based on the results of these experiments the increase in urinary phosphorus may have contributed to the inhibiting foreign body stone formation in a previous in vivo model. The decrease in urinary citrate could explain the augmentation of calcium phosphate stone formation previously reported.

Sodium pyruvate, potassium pyruvate, pyruvic acid, sodium bicarbonate and potassium bicarbonate were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) in order to determine their effects in preventing lithogenicity. Male Wistar-strain rats who had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the sodium and potassium pyruvate groups had, however, almost no stones in the urinary system. Rats in the bicarbonate and pyruvic-acid groups showed slightly less effect than those in the pyruvate groups. Urinary oxalate excretion was high in all the groups during the experiment. The urinary oxalate concentration was relatively higher in the sodium-pyruvate group, and significantly higher in the potassium-pyruvate group, than in the glycolic-acid group. Urinary citrate excretion was high both in the pyruvate and bicarbonate groups; the urinary citrate concentration was, however, significantly higher in the pyruvate groups than in the bicarbonate groups at the fourth experimental week. The urinary calcium and magnesium concentrations were irrelevant to the diets administered. Therefore, it can be concluded that pyruvate salts inhibit urinary calculi formation, not by decreasing oxalate synthesis, but by increasing the urinary citrate concentration; bicarbonate salts work in the same manner, but a little less effectively.

Pyrophosphate, citrate and magnesium, inhibitors of hydroxyapatite crystal growth, were studied using a seeded crystal growth system of constant composition at pH 5.80, 6.60 and 7.40. With this technique, crystal growth was studied at constant supersaturation at different pH values without the induction of other calcium phosphate phases. One inhibitor unit (that concentration of material that results in a reduction of 50 per cent in the growth rate from control) was calculated using the Langmuir adsorption isotherm. Pyrophosphate and citrate increased inhibitor activity with decreasing pH, whereas magnesium increased inhibitor activity with increasing pH. These data suggest that, at the urinary concentrations of these inhibitors, pyrophosphate is the most potent inhibitor, citrate less, and magnesium least. Pooled urine collections were studied using the same system and were found to have decreased inhibitor activity as pH decreased. This suggests that other modulators of hydroxyapatite, either promoters or inhibitors, are active in this system at the pH values studied.

From the analysis of various urinary constituents and the estimation of urinary saturation of stone-forming salts, it is now possible to identify risk factors responsible for or contributing to stone formation. Metabolic factors included calcium, oxalate, uric acid, citrate and pH. Environmental factors were total volume, sodium, sulfate, phosphate and magnesium. Physicochemical factors represented saturation of calcium oxalate, brushite, monosodium urate, struvite and uric acid. A scheme for graphic display of risk factors was developed to allow ready visual recognition of important risk factors presumed to cause stone formation. This graphic display had diagnostic use as well as practical value in following response to treatment. For example, a low urinary pH and high urinary concentration of undissociated uric acid could be discerned readily in cases of uric acid lithiasis, as were high urinary pH and exaggerated urinary supersaturation of struvite in cases of infection lithiasis. In a patient with absorptive hypercalciuria and hypocitraturia treatment with thiazide and potassium citrate could be shown to abolish high risks (hypercalciuria, hypocitraturia and relative supersaturation of calcium oxalate) displayed before treatment.

The diurnal variations of urine composition with respect to calcium, magnesium, oxalate, citrate and inhibition of calcium oxalate crystal growth were studied in patients with recurrent calcium oxalate stone disease. There was considerable variation in the excretion of the different urine constituents with meal-related peaks, which was most pronounced for calcium. The highest concentration of calcium was observed before noon, and between 7 and 11 p.m. Oxalate concentration was highest between 6 and 10 a.m. Consequently, the highest levels of supersaturation were recorded between 6 and 10 a.m., and 6 and 10 p.m. The inhibition index was at the highest level during the first morning hours and could be important in counteracting crystal growth at that time. The risk of exceeding a theoretical formation product of calcium oxalate appeared to be low, with a 24-hour urine volume more than 2,000 ml.