Urinary Saturation Research Articles

A patient with Primary Hyperoxaluria who developed excessive pericardial effusion despite intensive dialysis

Primary hyperoxaluria type 1 (PH type 1) is a hereditary disorder with excessive production of oxalate caused by deficient liver specific enzyme alanine-glyoxylate aminotransferase (AGT). Increased oxalate production leads to calcium oxalate deposition in different organs and tissues, such as kidney, heart, nervous system, skin, bone and bone marrow. Early diagnosis is essential to prevent complications. Family history, urine oxalate assesment, oxalaemia, determination of oxalate deposits in tissues and genetic analysis are beneficial for diagnosis. Treatment should be started at early stages of the disease in order to decrease urinary saturation of calcium oxalate. High fluid intake, urinary crystallisation inhibitors and pyridoxine may be used. In chronic kidney failure patients renal replacement therapies are necessary, early transplantation is mandatory. We present a 30 year old man with PH type 1 who admitted with severe pericardial effusion, despite the fact that he was maintained both peritoneal dialysis and frequent hemodialysis.

Assessment of Urinary Inhibitor or Promoter Activity in Uric Acid Nephrolithiasis

We assessed decreased inhibitor activity or increased promoter activity in the urine of idiopathic uric acid stone formers compared to nonstone formers independent of urinary pH. A total of 30 idiopathic uric acid stone formers, and 9 obese and 12 lean nonstone formers collected 24-hour urine while on a metabolic diet. Three urine aliquots per subject were used to assess spontaneous nucleation (de novo crystal formation), crystal growth using a 0.1 mg/ml anhydrous uric acid seed and steady-state uric acid solubility (the maximum amount of uric acid dissolvable in urine) using a 5 mg/ml uric acid seed. All experiments were performed for 6 hours at a constant pH of 5.0. Uric acid concentration was measured in filtered aliquots at 0, 3 and 6 hours. At baseline 24-hour urinary pH was significantly lower and uric acid saturation was significantly higher in idiopathic uric acid stone formers. No significant spontaneous nucleation developed and similar uric acid steady-state solubility was reached in the 3 groups. Idiopathic uric acid stone formers and lean nonstone formers showed a similar decrease in uric acid concentration during crystal growth. Obese nonstone formers started with a higher uric acid concentration and consequently demonstrated a greater decrease in the uric acid concentration for crystal growth. This study suggests that there is no significant difference between idiopathic uric acid stone formers and nonstone formers in promoter or inhibitor activity in whole urine against uric acid stone formation when urine pH is maintained constant. The findings suggest that uric acid stone formation is dictated by high urinary saturation with respect to uric acid, which is driven primarily by low urine pH.

Renal calculi in children

Abstract An increasing number of paediatric patients of all ages with renal calculi are being seen in outpatient clinics worldwide. This is attributed to changes in environmental factors like diet, fluid intake and obesity. In children however, genetic and/or metabolic disorders are still the main reason for kidney stones. Next to hypercalciuria, which is generally considered to be the most frequent risk factor, other lithogenic or stone-inhibitory disorders like hypocitraturia or hyperoxaluria and a variety of renal tubular diseases have to be evaluated by urine and/or blood analysis. Non-specific symptoms like growth retardation, intestinal malabsorption or bone demineralization are to be considered not only to avoid further complications, but for diagnostic purposes. In preterm infants a high incidence of nephrocalcinosis is observed. These infants often have a combination of immature kidney function or medication that leads to relative hypocitraturia. Concise evaluation to diagnose the underlying patho-mechanism as early as possible is mandatory in all paediatric patients. In more than three-quarters of children a metabolic basis of urolithiasis/nephrocalcinosis will be found. Early treatment by reducing urinary saturation index by increasing fluid intake, by providing crystallization inhibitors, but also by disease specific medication prevents recurrent kidney stones and/or progressive nephrocalcinosis and therefore deterioration of renal function.

Urinary calculi and infection

Infection urinary stones resulting from urease-producing bacteria are composed by struvite and/or carbonate apatite. Bacterial urease splits urea and promotes the formation of ammonia and carbon dioxide leading to urine alkalinization and formation of phosphate salts. Proteus species are urease-producers, whereas a limited number of strains of other Gram negative and positive species may produce urease. Ureaplasma urealyticum and Corynebacterium urealyticum are urease-producers that are not isolated by conventional urine cultures, but require specific tests for identification. Primary treatment requires surgical removal of stones as complete as possible. Extracorporeal and endoscopic treatments are usually preferred, while open surgery is actually limited to few selected cases. Residual stones or fragments should be treated by chemolysis via ureteral catheter or nephrostomy or administration of citrate salts in order to achieve a stone-free renal unit. Postoperatively, recurrent urinary tract infection should be treated with appropriate antibiotic treatment although long-term antibiotic prophylaxis can cause resistance. Urinary acidification has been proposed for the prophylaxis of infection stones, but long-term acidification is difficult to achieve in urine infected by urease-producing bacteria. Urease inhibitors lead to prevention and/or dissolution of stones and encrustations in patients with infection by urea-splitting bacteria, but their use is limited by their toxicity. The administration of citrate salts involves an increase of the value of nucleation pH (pHn), that is the pH value at which calcium and magnesium phosphate crystallization occurs, in a greater way than the corresponding increase in the urinary pH due to its alkalinizing effect and resulting in a reduction of the risk of struvite crystallization. In conclusion prevention of the recurrence of infection stones can be achieved by an integrated approach tailored on the single patient. Complete clearance of the stone must be achieved by primary surgical procedure and residual fragments should be extensively treated. In the case of persistent infection, conservative measures, such as acidification and urease inhibitors or citrate administration, should be adopted to minimize its effect on urinary saturation with respect to struvite.

Animal Protein and the Risk of Kidney Stones: A Comparative Metabolic Study of Animal Protein Sources

We compared the effect of 3 animal protein sources on urinary stone risk. A total of 15 healthy subjects completed a 3-phase randomized, crossover metabolic study. During each 1-week phase subjects consumed a standard metabolic diet containing beef, chicken or fish. Serum chemistry and 24-hour urine samples collected at the end of each phase were compared using mixed model repeated measures analysis. Serum and urinary uric acid were increased for each phase. Beef was associated with lower serum uric acid than chicken or fish (6.5 vs 7.0 and 7.3 mg/dl, respectively, each p <0.05). Fish was associated with higher urinary uric acid than beef or chicken (741 vs 638 and 641 mg per day, p = 0.003 and 0.04, respectively). No significant difference among phases was noted in urinary pH, sulfate, calcium, citrate, oxalate or sodium. Mean saturation index for calcium oxalate was highest for beef (2.48), although the difference attained significance only compared to chicken (1.67, p = 0.02) but not to fish (1.79, p = 0.08). Consuming animal protein is associated with increased serum and urine uric acid in healthy individuals. The higher purine content of fish compared to beef or chicken is reflected in higher 24-hour urinary uric acid. However, as reflected in the saturation index, the stone forming propensity is marginally higher for beef compared to fish or chicken. Stone formers should be advised to limit the intake of all animal proteins, including fish.

Urinary saturation: casual or causal risk factor in urolithiasis?

To assess (i) the extent to which urinary supersaturation (SS) has successfully discriminated between stone formers and healthy individuals (N), (ii) whether absolute SS has diagnostic worth and (iii) whether high SS is the fundamental cause of stone formation per se. Google Scholar was used to identify studies in which urinary compositional data had been determined. In those cases where SS values were not given, or where other risk indices had been reported, they were (re-)calculated. Collected data were termed 'global' but were then 'filtered' according to stone type and protocols used for SS calculations. SS distribution plots for calcium oxalate, brushite and uric acid were constructed. Data were statistically analysed using the unpaired t-test and Mann-Whitney test. In all, 47 studies yielded 123 SS values for healthy individuals and 122 values for stone formers. The mean and median SS values were significantly greater in stone formers compared with healthy individuals in all but one of the comparisons. Wide variations in SS occurred for healthy individuals and stone formers. The two groups could not be separated. Absolute SS has no diagnostic worth. It is impossible to quantify the meaning of a 'high' SS value. Urines cannot be identified as originating from healthy individuals or stone formers based on their SS. SS should be determined in clinical and research settings for relative comparisons during the assessment of treatment efficacies. This study provides a compelling argument for SS being a casual factor rather than a causal one.

Body Fat Content and Distribution and Urinary Risk Factors for Nephrolithiasis

Obesity is associated with a higher risk of nephrolithiasis. However, it is not known whether higher body fat mass or abnormal fat distribution influences stone risk independent of dietary factors. In this cross-sectional study, non-stone-forming men with no known kidney disease and with a wide range of body weight collected a 24-hour urine specimen while consuming a fixed metabolic diet. They underwent dual-energy x-ray absorptiometry to assess body composition and fat distribution. Urinary risk factors for nephrolithiasis and urine saturation with respect to calcium oxalate and uric acid (assessed as supersaturation index [SI]) were correlated with various measures of adiposity. Study participants included 21 men with a mean age of 52.1 years, mean weight of 91.1 kg, and mean total fat mass of 24.3 kg. Twenty-four-hour urine pH and SI uric acid were more closely correlated with fat mass than with lean mass or total body weight. Both 24-hour urine pH and SI uric acid were also significantly correlated with truncal fat mass but not with leg fat mass. Moreover, there was a significant negative correlation between truncal/leg fat mass and NH4(+)/net acid excretion ratio (R=-0.62; P=0.009). However, there was no significant association between SI calcium oxalate and body weight, lean mass, fat mass, trunk fat mass, or leg fat mass. The association between 24-hour urine pH and SI uric acid and various measures of adiposity suggest that total body fat and trunk fat are more strongly associated with risk factors for uric acid stone formation than are total body weight and lean body mass. Under a controlled metabolic diet, adiposity is not associated with risk factors for calcium oxalate stones. Further studies are needed to confirm these findings in larger populations that include women and patients who form stones.

Bariatric Surgery and Effects on Calcium and Bone Metabolism

With the increasing epidemic of obesity in the United States as well as abroad, bariatric surgery has emerged as the most effective and sustained treatment for reduction. This treatment modality has been well recognized to diminish the risk of cardiovascular morbidity and mortality and ameliorate diabetes mellitus. However, with time, derangement in mineral metabolism has emerged as a major complication in this population. Population-based study has shown increased prevalence of bone fractures and kidney stone formation following bariatric surgery. The risk appears to be more specific after Roux-en-Y gastric bypass procedures, the most common surgical approach among this population. Over the past decade, there have been advances in the understanding of pathophysiologic mechanisms of both bone loss and kidney stone disease in these patients. The understanding of these underlying pathophysiologic mechanisms may lead to the development of drug therapies that ameliorate this complication. Unfortunately, at the present time, there is no hard data on any specific treatment showing decreased incidence of fragility fractures or kidney stone passage. However, some studies suggest that calcium and vitamin D supplementation may decrease bone loss and bone turnover, and as a result, increase bone mineral density in this population. However, there is concern with the development of kidney stone formation following such an approach. A novel treatment approach would be the use of effervescent potassium calcium citrate that not only prevents complications of bone loss but may diminish the risk of kidney stone formation. Despite preliminary results showing the effectiveness of this drug in the reduction in the parathyroid hormone, bone turnover, and improvement in the urinary saturation marker showing effectiveness against calcium oxalate and uric acid stones, there is no hard data available to support the effectiveness of this treatment in the reduction in fragility fractures or kidney stone incidence. Such studies to explore this effect must be considered in the future.

Demographic characteristics and metabolic risk factors in Croatian children with urolithiasis

The aim of this study was to assess demographic data, clinical presentation, metabolic features, and treatment in 76 children with urolithiasis presented from 2002 to 2011. Urolithiasis is responsible for 2.5/1,000 pediatric hospitalizations, with new cases diagnosed in 1.1/1,000 admissions. From the observed period, two-fold rise of incidence rate was observed. Compiling the data from other pediatric institutions in our country, we estimated present overall incidence rate in Croatia as 6.5/100,000 children under 18 years. There were 41 boys and 35 girls (ratio 1.17:1). The mean age at diagnosis was 9.7 (range 0.8-16) years and follow-up duration was 5.3 (range 1.8-10) years. Renal colic (75.0 %) and hematuria (57.89 %) were the main symptoms. In 65.78 % of children, stones were unilateral. Stones were located in kidney in 52.63 %, in the ureter in 26.32 %, and in bladder in 6.58 % cases. Stone analysis showed calcium oxalate in 75.0 % of the cases. Associated urinary tract abnormalities were found in 19.73 % children. Most common metabolic disturbances were hypercalciuria (47.37 %) and idiopathic or mild hyperoxaluria (18.42 %). Urine saturation (EQUIL2) was elevated in 61.84 % cases. Spontaneous stone evacuation occurred in 51.21 % children. Extracorporeal shock wave lithotripsy, surgical evacuation, and endoscopic removal of calculi were performed in 21.0, 6.58, and 5.26 % of cases, respectively. Follow-up conservative therapy, consisting of fluid/diet recommendations and additional potassium citrate and/or chlorothiazide in children with increased risk, was sufficient for stone recurrence prevention in 92.1 % of children. In conclusion, the study gave insight in epidemiology and metabolic disturbances of urinary stone disease in Croatian children.

PROGNOSTICATION OF BILATERAL NEPHROLITHIASIS DEVELOPMENT RISK

The study involved 653 patients with nephrolithiasis. A multivariate based on discriminant analysis model predicting the risk of bilateral nephrolithiasis development was constructed. Clinical testing revealed high ability of the proposed mathematical model for predicting the development of bilateral nephrolithiasis. The relative risk criterion is highly informative to predict the risk of bilateral nephrolithiasis development. The signs of the high-risk are: urine pH rise over 6.1, concentration of the urine magnesium decrease under 2.26 mmole/l, level of the urine saturation with calcium oxalate over 3.27 and the relative tubular reabsorption under 97.5 %.

Rezidivierende Nephrolithiasis – wie weiter?

Nephrolithiasis is a common disease with a high recurrence rate. It is associated with a significant morbidity for an individual patient, but also an immense socioeconomic burden. A better understanding and recognition of underlying risk factors and prevention strategies are therefore of great importance. The evaluation for metaphylaxsis consists of a thorough patient history, metabolic examination of blood and urine, imaging of the kidney and urinary tract, and whenever possible a stone analysis. On the basis of the results, preventative measures can be performed. Therapeutic goals in stone prevention are to reduce the urine saturation of stone forming salts, to increase the urine concentration of stone formation inhibitors, and if necessary, the modification of urine pH. A dietary modification is the cornerstone of a successful metaphylaxis.

Urine saturation and promoter/inhibitor parameters and ratios in renal stone disease caused by ceftriaxone

Abstract During ceftriaxone treatment of subdural empyema caused by Streptococcus intermedius urinary and biliary stones were noticed. Increased levels of urinary calcium excretion were detected during ongoing treatment in comparison with 2 months check-up. There were no significant changes in the promoter/inhibitor urolithiasis parameters, oxalate, citrate, urate, cistine, glycosaminoglycans or their ratios. Urine saturation was calculated using EQUIL 2 computer programme (calcium oxalate, brushite) and it was normal. Probable trigger for the ceftriaxone/calcium hydroxy carbonate phosphate mixture of stones was a critical boost of solubility products caused by ceftriaxone treatment and phospnate urine content with a subsequent large-scale spontaneous precipitation of crystals.

1210 Urinary Stone Disease in Children- a Single Croatian Center Experience

Urinary stone disease is not so rare in children. The aim of this study was to assess the demographic, clinical and biological characteristics, as well as outcome, of urinary stone...

Evaluation of Patients with Renal Colic that Present to an Emergency Department During the Month of Ramadan

Objective: Our goal was to study the effects of fasting and mean weather temperature on blood biochemical parameters and urine test results in a group of patients that present with renal colic to an emergency department during the month of Ramadan. Material and Methods: Patients who presented to our emergency department from August 1-29, 2011 with a diagnosis of renal colic were included in the study. Patient demographic characteristics, major complaints, laboratory values and the average temperature of the day were recorded. Results: During the 29-day period, 61 patients were diagnosed with renal colic. Thirty-five patients were fasting, while 26 of them were not. In the comparison of fasting and non-fasting patients, there were no statistically significant differences in terms of age, arterial blood pressure, body temperature, blood glucose level, serum urea and creatinine levels, urine erythrocytes, leukocytes, ketones and density or in the chief complaint (p>0.05). Conclusion: Low urine volume reflects low fluid intake or excessive fluid loss, and directly increases kidney stone risk by increasing the urinary saturation of stoneforming salts. Fasting may result in limited fluid intake and increase renal colic presentations by affecting blood chemistry and urine concentration. In this study, no significant differences were observed between fasting and non-fasting patients in terms of the mechanisms that can cause renal colic. (JAEM 2013; 12: 24-6)

Urinary Metabolic Evaluation of Stone Formers—A Malaysian Perspective

To investigate the urinary metabolic excretion pattern among local stone formers given the great differences in the intrinsic and extrinsic risk factors as well as the urinary metabolic excretions compared with other populations. Thirty urinary stone formers out of an initial 62 recruited provided a complete 24-hour urine sample for metabolic evaluation. Student's t-test and Pearson correlation test were used for the statistical analysis. Urinary volume (1719 ± 712 vs 1215 ± 575, P < .05) and oxalate excretion (0.386 ± 0.111 vs 0.306 ± 0.104, P < .05) were significantly higher among stone formers than controls. Other commonly studied urinary parameters and urinary melamine did not differ significantly between the 2 groups. Similarly, the calcium/citrate ratio was unable to discriminate the stone formers from their controls. Hypocitraturia was the most prevalent urinary abnormality found in stone formers and low urinary citrate excretion was a general phenomenon in both stone formers and controls. Comparing within the stone formers cohort, the recurrent stone formers had a significantly higher urinary saturation and calcium excretion than their first-time stone former counterparts. Elevated urinary oxalate level was the most important urinary risk factor among the local stone formers. A low urinary citrate excretion appeared to be a general phenomenon among the studied cohorts.

Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load

Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.

Biochemical control of bone loss and stone-forming propensity by potassium-calcium citrate after bariatric surgery

Background Patients undergoing Roux-en- Y gastric bypass (RYGB) surgery are prone to developing bone loss and kidney stones. The goal of the present study was to test the hypothesis that an effervescent formulation of potassium calcium citrate (PCC) would avert metabolic complications by providing bioavailable calcium and alkali. Methods A total of 24 patients with RYGB underwent a 2-phase crossover randomized trial comparing PCC and placebo. During the last 2 days of each 2-week phase, the serum and 24-hour urine samples were analyzed for calcium and bone turnover markers, acid base status, and urinary stone risk factors. Results Compared with placebo, PCC marginally reduced the serum parathyroid hormone level and significantly decreased urinary deoxypyridinoline by 12% ( P <.001) and serum type 1 collagen C-telopeptide by 22% ( P <.01). PCC significantly increased the net gastrointestinal alkali absorption, citrate, and pH and significantly lowered the urinary net acid excretion ( P <.001). The urinary saturation of uric acid decreased significantly ( P <.001). The supersaturation of calcium oxalate and brushite did not change despite an increase in calcium and pH. In untreated urine samples with citrate concentrations altered to mimic those of placebo and PCC, calcium oxalate agglomeration was significantly inhibited by PCC. Conclusion In RYGB patients, PCC supplementation inhibited bone resorption by providing bioavailable calcium, reduced the urinary saturation of uric acid, and increased the inhibitor activity against calcium oxalate agglomeration by providing alkali that increased urinary pH and citrate.

Effect of n-3 Fatty Acid Supplementation on Urinary Risk Factors for Calcium Oxalate Stone Formation

Findings are inconsistent in a few studies of the effect of n-3 fatty acid supplementation on urinary calcium and oxalate excretion in stone formers. We evaluated the physiological effects of supplementation with eicosapentaenoic acid and docosahexaenoic acid on urinary risk factors for calcium oxalate stone formation under standardized conditions. We studied 15 healthy subjects initially while consuming a standardized diet for 5 days (control phase). During consecutive intervention phases 1-5-day standardized diet, 2-20-day free diet and 3-5-day standardized diet participants received 900 mg eicosapentaenoic acid and 600 mg docosahexaenoic acid daily. While ingesting the standardized diets, daily 24-hour urine samples were collected. After short-term supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 1 we noted no changes in urinary parameters compared to the control phase. After 30-day supplementation with eicosapentaenoic acid and docosahexaenoic acid in phase 3 relative supersaturation with calcium oxalate decreased significantly by 23% from a mean ± SD of 2.01 ± 1.26 to 1.55 ± 0.84 due to significantly decreased urinary oxalate excretion (p = 0.023). Other urinary variables were not affected by supplementation. Results show that 30-day n-3 fatty acid supplementation effectively decreases urinary oxalate excretion and the risk of calcium oxalate crystallization. The mechanism of the physiological effect may be decreased cellular oxalic acid exchange attributable to an altered fatty acid pattern of membrane phospholipids with concomitant changes in oxalate transporter activity. Calcium oxalate stone formers may benefit from long-term n-3 fatty acid supplementation.

Comparison of Semi-Empirical and Computer Derived Methods for Estimating Urinary Saturation of Calcium Oxalate

Estimating calcium oxalate saturation in human urine is critical for nephrolithiasis clinical research and practice. The Joint Expert Speciation System (Mayhem Unit Trust and Council for Scientific and Industrial Research, Pretoria, South Africa) computer program has questioned the validity of the widely used EQUIL 2 program in estimating calcium oxalate urinary saturation. To attempt resolution the computer model based supersaturation index (by the Joint Expert Speciation System) and the relative saturation ratio (by EQUIL 2) were compared with the experimentally derived activity product ratio, that is the ratio of activity products before and after incubating urine with synthetic calcium oxalate. To determine the experimental conditions required to attain calcium oxalate steady state solubility the filtrate concentration product of calcium and oxalate was determined after incubating 8 urine samples with 2 to 15 mg/ml calcium oxalate for various intervals. In 20 urine samples the activity product ratio of calcium oxalate was compared with the relative saturation ratio and the supersaturation index. Steady state solubility occurred after incubating 15 mg calcium oxalate per ml urine for 72 hours. The mean +/- SD supersaturation index of 4.92 +/- 2.57 in the original urine samples closely approximated the activity product ratio of 5.08 +/- 3.10 but the relative saturation ratio of 7.47 +/- 3.89 was significantly higher than the activity product ratio. The supersaturation index was recalculated after omitting soluble complexes recognized by the Joint Expert Speciation System but not by EQUIL 2, including Ca(2)H(2)(PO(4))(2) and (CaCitPO(4))(4-). The corrected supersaturation index was compared with the relative saturation ratio. After correction the supersaturation index increased to 7.28 +/- 3.81, which was not significantly different from the relative saturation ratio. The Joint Expert Speciation System is more accurate than EQUIL 2 to estimate calcium oxalate saturation, probably by accounting for Ca(2)H(2)(PO(4))(2), (CaCitPO(4))(4-), and other minor complexes of calcium and oxalate.

Comparison of Semi-Empirical and Computer Derived Methods for Estimating Urinary Saturation of Brushite

The Equil 2 computer program has been questioned by the new Joint Expert Speciation System program (Mayhem Unit Trust and Council for Scientific and Industrial Research, Pretoria, South Africa) for estimating the urinary saturation of stone forming salts to gauge the propensity for stone formation. To attempt resolution the supersaturation index according to the Joint Expert Speciation System and the relative saturation ratio according to Equil 2 were compared with the semi-empirically derived concentration-to-product ratio. Data were obtained from a recent article in The Journal of Urology(R), in which pH, calcium and citrate were varied over a wide range in 72 urine samples. We calculated the relative saturation ratio and the supersaturation index of brushite, and compared them with the available concentration-to-product ratio derived from the growth or dissolution of synthetic brushite. The mean concentration-to-product ratio did not differ from the supersaturation index but the concentration-to-product ratio and the supersaturation index were significantly lower than the relative saturation ratio (p <0.004). On the saturation value and urinary variable plot the relative saturation ratio could be readily distinguished from the concentration-to-product ratio because it was consistently and significantly higher. While the supersaturation index pattern was similar to the concentration-to-product ratio, the supersaturation index was slightly lower at high urinary pH and calcium, and slightly higher at lower urinary pH and calcium (p <0.001). When the Ca(2)H(2)(PO(4))(2) complex was deleted from the Joint Expert Speciation System, the corrected supersaturation index was not significantly different from the relative saturation ratio determined by Equil 2. The relative saturation ratio overestimates brushite saturation by about 80%. The supersaturation index yields a good approximation of brushite saturation at modest degrees of saturation but it overestimates saturation at low pH or calcium (low saturation) and underestimates it at high pH or calcium (high saturation).